Hereditary nephritis (Alport syndrome) in children. Alport syndrome treatment. Alport syndrome - a hereditary disease of nephritis Autosomal dominant Alport syndrome

Alport syndrome is a hereditary disorder that manifests itself in the early onset of renal failure, hearing loss and vision loss.

This syndrome is a hereditary form of kidney inflammation - jade. It's connected with mutation in the protein gene, called collagen.

The disorder is rarely observed. More often it occurs the stronger sex.

Women can pass the gene for the disorder to their children, even if they are asymptomatic.

TO risk factors relate:

• Severe stage of kidney disease in male relatives;
• Family history of the disorder;
• Hearing loss before 30.

Clinical picture

Symptoms of the disorder may already appear in the first year of life crumbs, but most often manifested at 3–5 years old.

For most children, the predisposing condition is previous infection. Due to the lack of manifestation, the disease may be detected accidentally based on urine tests.

This type of nephritis in children can occur as hematuric glomerulonephritis or pyelonephritis.

Initial stage deviations are typical no complaints. During normal kidney function, only changes in urine: red blood cells, white blood cells, and protein appear.

Development of the disorder combined with nephrotic syndrome and high blood pressure. Patients have the following symptoms:

• weakness,
• headaches,
• deterioration of vision, hearing,
• decrease in pressure,
• pale skin,
• lethargy.

The difference between Alport syndrome in children and other forms of nephritis is damage to the auditory nerve.

The difficulty is that it can be identified only after audiometry, which is carried out after 7 years. Only 20% of children have visual impairment, and thrombocytopenia is observed only in isolated cases.

Deafness is more common in boys - they experience a much faster increase in blood pressure and a progressive decline in kidney function.

By the age of 18 the development of the disease causes a complete set manifestations of renal failure:

• pale skin,
• dry mouth,
• nausea,
• trembling of hands and fingers,
• a decrease in the volume of urine excreted or its complete absence,
• Sometimes there is aching in the muscles and joints.

Without timely implementation replacement therapy or transplantation of a diseased kidney The lifespan of a person will not exceed 40 years.

Forms of the syndrome:

Autosomal recessive

In this type of inheritance, the mutated gene appears only when one recessive gene is received from the father and the second from the mother.

Risk the appearance of an unhealthy baby is 25%.

Sick boys and girls are born equally often.

Parents of sick children may appear healthy, but are carriers of an unhealthy gene.

Autosomal dominant

Dominant inheritance, based on the X chromosome, is where the effect of a dominant unhealthy gene occurs regardless of gender.

More difficult the disorder goes away in boys.

One of the child's parents is certainly not healthy. Among the children of men, sons are healthy, and daughters are sick. Women pass on the mutated gene to 50% of their sons and daughters.

How to diagnose the disease?

The syndrome can be assumed based on pedigree information by the presence of the disorder in other relatives. To diagnose the disease it is necessary presence of three out of five indicators:

1. Hematuria or death from renal failure in the family;
2. Hematuria or proteinuria in relatives;
3. Detection of changes during organ biopsy;
4. Hearing loss;
5. Congenital visual impairment.

Diagnostics violations are carried out in the following ways:

• Collection and study of anamnesis;
• Physical method;
• Lab tests;
• Ultrasound examination,
• Computed tomography or magnetic tomography;
• Scintigraphy;
• Biopsy.

The distinctive diagnosis of the disorder consists of distinguishing between nephritis and nephropathy.

Is it possible to treat Alport syndrome?

There is no specific treatment. They attach great importance pressure control And protein restriction in diet when kidney function begins to decline.

As XHH develops, patients undergo hemodialysis treatment.

People with the syndrome are candidates for a kidney transplant, although in some situations Goodpasture's syndrome may appear after the transplant.

Therefore, donor selection must be done extremely carefully.

In the absence of specific treatment, the main goal is to slow the progression of kidney failure.

For children prohibited physical exercise, is appointed balanced diet.

Special attention is paid treatment of infectious foci.

Use of hormonal agents and cytostatics does not cause significant improvement in the condition. The main method of treatment remains organ transplant.

Poor prognosis for the course of the disease, which is characterized by the rapid development of end-stage renal failure, is likely in the presence of the following indicators:

• Male gender;
• High protein content in urine;
• Early appearance of kidney problems in relatives;
• Hearing loss.

When found hematuria without proteinuria and hearing loss The prognosis for the course of the disorder is favorable; insufficiency does not occur.

The course of the syndrome can be progressive And not progressive, the prognosis is positive in women without hearing changes.

Each patient has its own degree of development of the process in the kidneys.

In 50% of boys, the last stage of kidney failure occurs by age 30, and sometimes even by age 20. For others, the process develops more slowly, but ultimately causes kidney dysfunction.

For girls the disorder progresses more slowly and does not affect life expectancy, even taking into account persistent microhematuria.

Dialysis and organ transplant favor a more positive prognosis.

Video: What you need to know about hereditary diseases

Useful information about hereditary diseases, which will help avoid the development of many diseases in the unborn child. If you take these tips into account, the likelihood of having a child with hereditary disorders will be significantly reduced.

Alport syndrome is a hereditary disease in which the decline in kidney function constantly progresses. In addition, deafness and blindness develop along with the syndrome.

Such syndromes are caused by a gene located in the long arm of the X chromosome in the 21-22 q zone. Alport occurs when the structure of type IV collagen is disrupted - the protein that forms the basis of connective tissues and is responsible for making them strong and elastic. Thus, with the disease, a defect occurs in the collagen of the vascular walls of the kidneys, organs of Corti in the ears and lens capsules in the eyes.

Classification and symptoms

Hereditary nephritis has three variants:

In the first version Along with the syndrome, nephrotic syndromes, hematuria appear, deafness develops and the eyes are affected. In this case, nephritis progresses to chronic renal failure. Inherited in a dominant manner. The basement membranes are thinned and split, their structure is disrupted.

Second option develops along with nephritis and hematuric manifestations, but hearing does not decrease. Nephritis also progresses and reaches chronic renal failure. The basement membranes of the glomerular capillaries are also thinned.

Third type characterized by benign familial hematuria. The course of the disease is benign, chronic renal failure does not occur.

Alport syndrome in children can manifest itself quite different symptoms. Most often, manifestations of the disease become noticeable by 5-10 years. The first symptoms of Alport syndrome (isolated urinary syndrome) appear in the first three years of a child’s life. Most often, the disease is discovered accidentally during a routine examination of the baby. During this period, the baby feels absolutely normal, and only the urinary syndrome does not recede.

The main symptom of the disease is hematuria. It may manifest itself different degrees, and is ALWAYS observed! It may intensify during and after infectious lesions, which affect the respiratory tract, as well as during physical exertion. Especially excessive ones. Often, parents can sound the alarm after routine vaccinations - because they also provoke an exacerbation of hematuria.

Inconstancy of proteinuria is also noted, especially when the disease is just beginning to develop. And the more obvious the symptoms of the underlying disease become, the stronger the proteinuria. Sometimes leukocytes are found in urine sediment, but there are no bacteria in the urine.

Over time, partial kidney functions are disrupted, the patient’s condition becomes worse - intoxication is noted (patients turn pale, quickly get tired, complain of headaches), weakness appears in the muscles, signs of hypertension increase, hearing and vision are impaired.

At the beginning of the disease, hearing loss is determined only during a special test - audiography.

Hearing loss is possible at any age. Most often, deafness occurs in 6-10 year old children, and in some cases it occurs faster than urinary syndrome.

Approximately 20% of patients experience decreased vision. Most often this happens due to damage to the lens. Very often, members of a family in which Alport syndrome is susceptible suffer from myopia.

Many children have hereditary nephritis, especially if it develops into kidney failure. They are lagging behind in physical development. Arterial hypertension often develops against the background of kidney failure.

Most patients with Alport syndrome have stigmata of dysembryogenesis (more than seven). They manifest themselves as small external deviations, but have virtually no effect on the functions of the body. Such stigmas include epicanthus (folds on the inner corner of the eye), deformed ears, high palate, fused fingers, or an increased number of them.

So, hereditary nephritis occurs in stages - first in a latent form, when the clinical symptoms are hidden and the urinary syndrome is minimally manifested. Next, decompensatory processes begin, during which the functioning of the kidneys decreases and manifest clinical symptoms appear.

Diagnostics

Hereditary nephritis in children is easy to assume if the pedigree is known and the same symptoms were present in other family members. To diagnose a disease, at least three of the possible five criteria must be met:

1. Hematuria in relatives, or death due to chronic renal failure
2. Hematuria and/or proteinuria in relatives
3. Changes of a specific nature that are determined by biopsy
4. Deafness
5. Pathological vision (most often congenital)

When it comes to hereditary diseases, including congenital ones, diagnosis should always be comprehensive. Particular care should be taken when compiling the child’s pedigree.

Clinical and genetic research methods are mandatory for Alport syndrome and must certainly include a medical history, as well as a general examination of the patient.

In the compensatory stages of the disease, it can only be detected based on hereditary burden, hypotension, multiple stigmas and altered urinary syndrome.

Differential diagnosis is also extremely necessary. First of all, you should not confuse the hematuric form of glomerulonephritis with Alport, otherwise the therapy chosen as a result of an incorrect diagnosis will be completely ineffective. In addition, dysmetabolic nephropathy and other kidney diseases should be distinguished from Alport syndrome.

Therapeutic measures

First of all, the patient should be protected from excessive physical strain; children with pathology are exempted from physical education lessons. Frequent and long walks in fresh air are recommended. The dietary regimen must be complete, containing proteins, fats and carbohydrates. But nutrition is developed and selected taking into account all kidney functions.

In case of Alport syndrome, it is necessary to identify and sanitize all possible infectious foci in a timely manner.

Among the drugs most often used are ATP, cocarboxylase, pyridoxine (up to 50 mg/day), and carnitine chloride.

Hematuria is treated using herbal medicine. For these purposes, stinging nettle, chokeberry juice and yarrow are used. For example, it is possible to prepare something like this tinctures. Mix stinging nettle with shepherd's purse and horsetail. You need 10 g of all herbs. Mix the mixture well, measure out two small spoons, pour two glasses of boiling water and leave to steep for at least 8 hours. After this, we pass it through gauze, add water to the glasses and take 100 ml every other day.

Patients with chronic renal failure are indicated for hemodialysis, and in case of chronic renal failure, an organ transplant is almost always required.

There is no specific therapy that would relieve hereditary nephritis. Therapeutic measures pursue one goal - to prevent and slow down the decline in kidney function.

A prerequisite is to limit contact of sick children with infectious patients, as well as reduce the risk of developing acute respiratory infections in such children. Children are not vaccinated for hereditary nephritis, although epidemiological vaccination is possible.

Hormones and immunosuppressive drugs for the syndrome do not have the desired effects. However, if too long time Using cyclosporine A and ACE inhibitors can achieve some positive effect - reduce the level of proteinuria, somewhat slow down the progression of the disease.

But the use of drugs that improve metabolic processes is indicated. In this regard, pyridoxine, cocarboxylase, ATP, vitamins A and E may be effective. The above drugs improve the general condition and reduce tubular dysfunction. They are accepted in special courses three times a year.

However, the most effective method The only treatment for hereditary nephritis today is kidney transplantation. As a rule, the disease does not recur in transplanted organs. And only occasionally (in about 5% of cases) does nephritis develop. However, it is associated with antigens to the glomerular basement membrane.

Prenatal diagnosis and genetic engineering treatment are extremely important and promising. IN last years Many experiments were carried out on animals that showed and proved the effectiveness of the transfer of normal genes that are responsible for the synthesis of type IV collagen a-chains into kidney tissue. After this, in almost all cases, normal collagen structures are synthesized.

Forecasting

It is difficult to predict anything with Alport syndrome. The only thing that can be said is that such forecasting is not always favorable. Especially if the patient is male, he has developed early kidney failure, has severe proteinuria, thickened glomerular basement membranes, and neuritis of the auditory nerves. The prognosis for benign familial hematuria is much more favorable.

It was first described by Zamelson and Dickinson (F. Samelsohn, W. H. Dickinson) in 1873 -1875. Later, Guthrie (L. G. Guthrie, 1902) suggested the existence of a special form of hereditary nephropathy, clinically similar to chronic nephritis. Alport followed the fate of members of several families, examined some of them who had previously been observed at Guthrie, and discovered deafness in many. Since 1961, hereditary nephritis combined with deafness has been called Alport syndrome [Williamson (D. A. Williamson)].

Etiology.

Alport syndrome is inherited in a dominant, sex-linked manner. The mutant gene is associated with the X chromosome, which can determine more severe course diseases in males. Whether the combination of clinical syndromes of kidney and hearing damage is associated with a mutation of one or more genes has not yet been established.

Pathological anatomy.

The morphological picture of the kidneys in Alport syndrome depends on the age of the patient and the period of the disease. The initial stage of the disease, according to puncture biopsy, is characterized by the absence of histological changes in the kidney tissue. An early pathological sign is the detection of red blood cells in the lumen of the renal tubules. Subsequently, infiltration of interstitial tissue appears (as a consequence of impaired metabolism and accumulation of metabolites, in particular lipoid substances, in the kidney tissue), glomerular damage in the form of endothelial proliferation, thickening of the basement membrane, interstitial fibrosis, and vascular hyalinosis.

In some cases, so-called foam cells are found. During this period, Alport syndrome. difficult to differentiate from acquired glomerulo- or pyelonephritis.

At histological studies In the inner ear, atrophy of the ganglion cells of the auditory system is detected.

Clinical picture.

The disease develops slowly. The earliest sign of Alport syndrome is hematuria; slight proteinuria is often noted, and leukocyturia is less common. Hematuria can occur in the first year of a child’s life, but most often it is detected at the age of 7–10 years by chance, during clinical examinations, against the background of intercurrent diseases. In Alport boys, the syndrome progresses steadily until the development of renal failure. Children are developmentally delayed. In girls and women, hereditary nephritis has a relatively more benign course, manifested by persistent hematuria, and renal failure is possible only during pregnancy.

Alport syndrome is characterized by the absence of an acute onset of the disease and extrarenal manifestations of nephritis. Edema and hypertension syndromes as a consequence of renal failure (but not the activity of the process) appear only in adolescence and in adults. Studies of protein, lipid metabolism, and nonspecific indicators of the immune process do not reveal pronounced changes. The functions of the adrenal cortex do not change. Immunological changes are characterized by an increase in the level of immunoglobulin G in the blood not only in the proband, but also in his relatives. Deafness develops later in the course of the disease or may be absent altogether. It is observed in 16% of patients. Less common are eye lesions (cataracts, spherophakia with secondary myopia, retinitis pigmentosa), and developmental defects urinary tract. X-ray examination reveals unilateral or bilateral pyelectasis in most patients.

Alport syndrome (AS) is an inherited type IV collagen disorder characterized by the combination of progressive hematuric nephritis with ultrastructural changes and sensorineural hearing loss. Visual disturbances are also common with this syndrome. Microhematuria detected in early dates life is constant characteristic feature diseases.

Recurrent episodes of gross hematuria occur in approximately 60% of patients under the age of 16 years, but are quite rare in adults. Over time, the disease develops and progresses with age, depending on the gender of the patient and the type of inheritance of the disease. is a late sign.

Bilateral sensorineural hearing loss, affecting high- and mid-frequency hearing, is progressive in children but may become apparent later. There are reports of several types visual disturbances, also progressing with age. Anterior lenticone is a cone-shaped protrusion of the front part of the lens. Spots appear on the retina of the eye yellowish color, which are asymptomatic. Both types of lesions are specific and are observed in approximately one third of patients. There are also reports of recurrent corneal erosions in patients with AS.

Morphology

Under light microscopy, renal tissue obtained from early stages SA, appears normal. Focal and segmental thickening of the capillary walls of the glomeruli, better identified by silver staining, become visible as the disease progresses. They are combined with nonspecific tubular lesions and interstitial fibrosis. Standard immunofluorescence is usually negative. However, weak and/or focal deposits of classes G and M and/or complement fraction S3 may be detected. The main damage is detected by the ultrastructural method. They are characterized by thickening (up to 800-1200 nm) with splitting and fragmentation of the lamina densa into several fibers forming a network like a basket. The changes may be fragmented (heterogeneous), alternating with areas of normal or reduced thickness. In general, the most prominent feature in children is an uneven alternation of very thick and very thin areas of the GBM. Diffuse thinning of the GBM is found in approximately 20% of patients with SA.

At the genetic level, SA is a heterogeneous disease: mutations of COL4A5 on the X chromosome are associated with X-linked SA, while mutations of COL4A3 or COL4A4 on chromosome 2 are associated with autosomal forms of the disease.

X-linked Alport syndrome.

Clinical symptoms.

The X-linked variant is the most common form of SA, characterized by a more severe course of the disease in male patients than in female patients, and the absence of transmission in the male line. Availability hematuria– a necessary criterion for diagnosis. gradually increases with age and can subsequently lead to the development of nephrotic syndrome. All male patients progress to end-stage renal disease. There are two types of SA - juvenile, in which ESRD develops around the age of 20 years in men with maternal transmission of the disease, and adult, characterized by a more variable course and development of ESRD around the age of 40 years. In heterozygous females, hematuria is detected only in adulthood. It is absent in less than 10% of women (carriers). The risk of developing ESRD in women under 40 years of age is about 10-12% (versus 90% in men), but increases after 60 years of age. Most heterozygotes never develop ESRD. Bilateral sensorineural hearing loss progresses in most male and some female patients. Changes in the organ of vision, anterior lenticonus and/or perimacular spots are observed in 1/3 of patients. In families with AS, women may experience diffuse esophageal leiomyomatosis, which also includes tracheal lesions bronchial tree and genital tract of women and sometimes congenital cataracts.

Molecular genetics made it possible to establish the characteristics of mutations in the COL4A5 gene. They cause differences in clinical manifestations, course and prognosis.

Autosomal recessive Alport syndrome

Alport syndrome is inherited in an autosomal recessive manner in approximately 15% of affected European families. This type of inheritance is more common in countries with more high level consanguineous marriages. Clinical symptoms and ultrastructural changes are identical to those observed in X-linked SA. However, some signs clearly indicate recessive inheritance: consanguineous marriages, severe disease in female patients, lack of serious illness in parents, microhematuria in father. The disease, as a rule, progresses early to ESRD, hearing impairment is almost always encountered, and not always - damage to the organ of vision.

Among heterozygotes, constant or intermittent microhematuria is noted.

Autosomal dominant Alport syndrome

Autosomal dominant inheritance, characterized by transmission through the male line, is rare. The clinical phenotype is the same for men and women. The course is milder than the X-linked form, with late and variable progression to the development of ESRD and hearing loss. Heterozygous mutations in the COL4A3 or COL4A4 genes have been identified in some families.

Diagnosis and treatment of Alport syndrome. Diagnosis of SA and determination of the type of inheritance are important for therapeutic management, prognosis and medical genetic counseling of patients and their families. The issue is easily resolved if hematuria is combined with deafness or eye lesions and if the hereditary history is sufficiently informative to establish the type of inheritance. Each incidentally discovered hematuria requires examination of other family members. Early onset of hematuria and detection of sensorineural hearing loss, lenticonus, or maculopathy upon careful examination may provide guidance regarding AS, but the mode of inheritance remains uncertain. Identification of mutations in the COL4A5, COL4A3, or COL4A4 genes is critical for disease diagnosis, but molecular analysis is expensive and time-consuming due to the large size of the type IV collagen gene and the wide variety of mutations.

It is important to differentiate Alport syndrome early from thin basement membrane disease (TBMD). This is best done on the basis of family history: the presence in the family of adult men over 35 years of age with hematuria and preserved renal functions with a high probability allows us to settle on the diagnosis of BTBM.

In the absence of hearing loss, diagnosis is quite difficult: if you do a renal biopsy too early (before 6 years), you may not see the changes characteristic of Alport syndrome, which will develop later, and electron microscopy is not available everywhere. In this regard, the introduction of an immunohistochemical method for determining the expression of various type IV collagen chains in renal tissue or skin is promising.

Sporadic hematuria with proteinuria, detected in the absence of extrarenal manifestations, is the reason for a renal biopsy to exclude other hematuric glomerulopathies (IgA nephropathy, etc.). Progression to end-stage renal disease is inevitable in X-linked AS in men and in all patients with autosomal recessive AS. To date, there is no specific treatment. The main treatment is blockade of the renin-angiotensin system to reduce and possibly slow progression. Kidney transplantation leads to satisfactory results, however, about 2.5% of all patients with AS develop anti-GBM due to formation of the donor's “other” GBM, which leads to graft rejection.

Alport syndrome is a hereditary disease that is directly characterized by a consistent decrease in kidney function, coupled with pathology of hearing and even vision. On currently in our country, this type of illness among the (mainly) child population is approximately 17: 100,000.

Main reasons

According to experts, Alport syndrome occurs due to abnormalities in a gene that is located in the long arm of the X chromosome in the so-called zone 21-22q. In addition, violation integral structure so-called type 4 collagen is also the cause of this disease. In science, collagen is understood as a protein that is a direct component connective tissue ensuring its elasticity and continuity.

Symptoms

Alport syndrome usually first appears in children aged five to ten years and manifests itself in the form of hematuria (blood in the urine). More often this diagnosis It is discovered randomly, that is, during the next examination by a specialist. In addition, Alport syndrome also manifests itself in the form of so-called stigmas of dysembryogenesis. These are relatively minor deviations that do not play a special role in the functioning of the main systems of the body. Doctors note the epicanthus (small fold at the inner corner of the eye), high palate, slight deformation of both ears and other signs. Consistency is also a sure sign of this disease, and hearing loss is much more often diagnosed in boys. All of the above symptoms are most often detected in adolescence, while the common chronic one makes itself felt only during adulthood.

Diagnosis

Alport syndrome in children is usually diagnosed based on evidence of the presence of this type of illness in other family members. For example, to confirm the disease, it is enough to meet three of the five criteria listed below:

• hearing loss;
• cases of death from chronic renal failure of close relatives;
• confirmation of hematuria in family members;
• vision pathologies;
• the presence of specific changes during kidney biopsy.

In the absence of specific therapy, doctors must first slow the progression of kidney failure. With a diagnosis such as Alport's disease, children are strictly prohibited from physical activity; they are prescribed. Important attention is paid to the sanitation of so-called infectious foci. Use in the treatment of cytostatics and various types hormonal drugs helps improve the condition. However, it is most often prescribed as the preferred method of treatment. It should be noted that when hematuria is detected without significant hearing impairment, the overall prognosis for the course of the disease is somewhat more favorable. In this kind of situation, renal failure is diagnosed extremely rarely.

Alport syndrome is a genetically determined inflammatory kidney disease, accompanied by damage to the auditory and visual analyzers. It's quite rare hereditary pathology, occurring in 1 in 10 thousand newborns. According to WHO, people with Alport syndrome make up 1% of all patients with kidney dysfunction. According to ICD-10, the disease has code Q87.8.

Alport syndrome affects the gene encoding the structure of the collagen protein located in the basement membrane of the renal tubules, inner ear and organ of vision. The main function of the basement membrane is to support and separate tissues from each other. Hereditary nonimmune glomerulopathy is manifested by hematuria, sensorineural hearing loss, and visual impairment. As the syndrome progresses, patients develop renal failure, which is accompanied by diseases of the eyes and ears. The disease is progressive and cannot be cured.

Hereditary nephritis or familial glomerulonephritis are names of the same pathology. It was first described in 1927 by British scientist Arthur Alport. He observed members of one family who suffered from hearing loss and had red blood cells in their urine tests. Several years later, eye lesions were identified in individuals with this disease. It was only in 1985 that scientists established the cause of such anomalies. It was a mutation of the gene responsible for the synthesis and structure of type IV collagen.

Most often, this disease causes severe renal dysfunction in males. Women can pass the mutant gene to their children without having clinical manifestations. The syndrome manifests itself from the first years of life. But most often it is found in children aged 3-8 years. In sick children, signs of kidney damage first appear. Problems with hearing and vision develop somewhat later. In late childhood and adolescence, severe kidney pathology, loss of vision and hearing develop.

According to the mode of inheritance of the anomaly, 3 forms of pathology are distinguished: X-linked dominant, autosomal recessive, autosomal dominant. Each form corresponds to certain morphological and functional changes in the internal organs. In the first case, the classic form develops, in which inflammation of the kidney tissue is manifested by blood in the urine and is accompanied by decreased hearing and vision. In this case, the disease has a progressive course, and kidney failure quickly develops. A histological feature of such processes is thinning of the basement membrane. In the second case, the congenital disease is much milder and is characterized by isolated inflammation of the kidneys with hematuria. The autosomal dominant form is also considered benign, has a favorable prognosis and is manifested only by hematuria or is asymptomatic.

Hereditary kidney inflammation is discovered by chance, during a medical examination or diagnostic examination of other diseases.

Etiology

The true etiopathogenetic factors of the pathology have not yet been fully studied. It is believed that Alport syndrome is a hereditary disease caused by a mutation of a gene located on the long arm of the X chromosome and encoding the type IV collagen protein. The main function of collagen is to ensure the strength and elasticity of connective tissue fibers. With this syndrome, damage to the vascular wall of the kidneys, organ of Corti, and lens capsule is noted.

The mutant gene is most often passed on from parents to children. There are main forms of inheritance of pathology:

• The dominant X-linked type of inheritance is characterized by the transmission of the affected gene from mother to son or daughter, and from father to only daughter. The syndrome is more severe in boys. Sick fathers give birth to healthy sons and sick daughters.
• The autosomal recessive type is characterized by receiving one gene from the father and a second from the mother. Sick children are born in 25% of cases, and equally often among both girls and boys.

In a family with hereditary diseases of the urinary system, the likelihood of having sick children increases significantly. If a sick child is born into a family where all members have perfectly healthy kidneys, the cause of the syndrome is a spontaneous genetic mutation.

Factors contributing to the development of the disease:

1. relatives with kidney pathologies;
2. consanguineous marriages;
3. changes in the immune system;
4. hearing loss at a young age;
5. acute infections of bacterial or viral origin;
6. vaccination;
7. physical stress.

The expression of the mutant gene in different individuals varies from weak to significant severity of the clinical manifestations of hereditary nephritis. The process of destruction of the basement membrane is directly dependent on the severity pathological process.

Pathogenesis

Pathogenetic links of the syndrome:

• violation of collagen biosynthesis or its deficiency,
• destruction of the basement membrane of the kidneys, inner ear and ocular apparatus,
• sprouting of collagen fibers types V and VI,
• damage to the renal glomeruli,
• immunonegative glomerulitis,
• glomerular hyalinosis, tubular atrophy and renal stromal fibrosis,
• glomerulosclerosis,
• accumulation of lipids and lipophages in the renal tissue,
• decrease in the blood level of Ig A, increase in IgM and G,
• decreased activity of T- and B-lymphocytes,
• impaired renal filtration function,
• dysfunction of the organ of vision and hearing,
• accumulation of toxins and metabolic products in the blood,
• proteinuria,
• hematuria,
• development of acute renal failure,
• death.

The disease develops gradually with renal symptoms. In the early stages of pathology, the kidneys work fully, and there are traces of protein, leukocytes and blood in the urine. Pollakiuria and nocturia are accompanied by hypertension and other signs of urinary syndrome. In patients, the calyces and pelvis of the kidneys dilate, and aminoaciduria occurs. After some time, hearing loss of neurogenic origin occurs.

Men are most susceptible to developing kidney dysfunction. If left untreated, death occurs between 15 and 30 years of age. Women usually suffer from a latent form of pathology with signs of hematuria syndrome and slight hearing loss.

Symptoms

Hereditary nephritis in children can occur according to the glomerulonephrotic or pyelonephrotic type. Clinical signs Alport syndrome is conventionally divided into two large groups - renal and extrarenal.

Main manifestations renal symptoms are: hematuria - blood in the urine and proteinuria - protein in the urine. Red blood cells appear in the urine of sick children immediately after birth. At first it is asymptomatic microhematuria. Closer to 5-7 years, blood in the urine becomes clearly visible. This is a pathognomonic sign of Alport syndrome. The intensity of hematuria increases after acute infectious diseases- ARVI, chickenpox, measles Active physical activity and preventive vaccinations can also provoke a significant increase in red blood cells. Boys develop proteinuria somewhat less frequently. Girls usually do not have this symptom. Loss of protein in the urine is accompanied by edema, increased blood pressure, and general intoxication of the body. Possible leukocyturia without bacteriuria, anemia.

As Alport's disease progresses, it is complicated by the development of renal failure. Its classic signs are dry, yellowish skin, decreased turgor, dry mouth, oliguria, tremor of the hands, aches in the muscles and joints. In the absence of proper treatment, a terminal stage of pathology occurs. In such cases, only hemodialysis will help maintain the vitality of the body. Timely replacement therapy or transplantation of a diseased kidney can prolong the life of patients.

Extrarenal symptoms include:

1. hearing loss caused by acoustic neuritis;
2. visual impairment associated with cataracts, changes in the shape of the lens, the appearance of white or yellow spots on the retina in the area of ​​the macula, myopia, keratoconus;
3. delay in psychophysical development;
4. birth defects – high palate, syndactyly, epicanthus, ear deformation, malocclusion;
5. leiomyomatosis of the esophagus, trachea, bronchi.

Nonspecific general intoxication signs of pathology include:

• headache,
• myalgia,
• dizziness,
• sharp fluctuations in blood pressure,
• dyspnea,
• frequent, shallow breathing,
• noise in ears,
• pale skin,
• frequent urge to urinate,
• dyspepsia,
• loss of appetite,
• disturbance of sleep and wakefulness,
• itchy skin,
• convulsions,
• chest pain,
• confusion.

Patients develop compensated glomerular and tubular failure, the transport of amino acids and electrolytes, the concentrating ability of the kidneys, acidogenesis are impaired, and the nephron tubular system is affected. As the pathology progresses, the signs of urinary syndrome are complemented by severe intoxication, asthenization and anemia of the body. Similar processes develop in boys who have the affected gene. In girls, the disease is much milder and they do not develop persistent kidney dysfunction. Only during pregnancy do girls suffer from the symptoms of the disease.

Complications of Alport syndrome develop in the absence of adequate therapy. In patients, signs of kidney failure increase: swelling of the face and limbs, hypothermia, hoarseness, oliguria or anuria appear. Secondary is often added bacterial infection– pyelonephritis develops or purulent otitis media. In this case, the prognosis is unfavorable.

Diagnostics

Pediatricians, nephrologists, geneticists, ENT doctors, and ophthalmologists are involved in the diagnosis and treatment of Alport syndrome.

Diagnostic measures begin with collecting anamnesis and listening to the patient’s complaints. Family history is of particular importance. Experts find out whether there were cases of hematuria or proteinuria in relatives, as well as cases of death from renal dysfunction. To make a diagnosis, genealogical analysis and obstetric history are important.

1. Specific damage to the basement membrane in patients is detected by biopsy results.
2. In general urine analysis - red blood cells, protein, leukocytes.
3. Genetic research - identifying gene mutations.
4. Audiometry detects hearing impairment.
5. An examination by an ophthalmologist can identify congenital vision pathologies.
6. Ultrasound examination of the kidneys and ureters, magnetic resonance imaging, X-ray and scintigraphy are additional diagnostic techniques.

Treatment

Alport syndrome is an incurable disease. The following expert recommendations will help slow down the development of kidney failure:

• Rational and fortified diet,
• Optimal physical activity
• Frequent and long walks in the fresh air,
• Sanitation of foci of chronic infection,
• Prevention of infectious diseases,
• Ban on routine vaccinations for sick children
• A herbal collection of nettle, yarrow and chokeberry is indicated for sick children with hematuria,
• Vitamin therapy and biostimulants to improve metabolism.

Proper nutrition consists of eating easily digestible foods with sufficient amounts of essential nutrients. From the diet of patients, salted and smoked foods, spicy and hot dishes, alcohol, and products with artificial colors, stabilizers, and flavors should be excluded. In case of impaired renal function, it is necessary to limit the intake of phosphorus and calcium. Such recommendations should be followed by patients throughout their lives.

Drug symptomatic therapy:

1. To eliminate hypertension, ACE inhibitors are prescribed - Captopril, Lisinopril and angiotensin receptor blockers - Lorista, Vasotens.
2. Pyelonephritis develops as a result of infection. In this case, antibacterial and anti-inflammatory medications are used.
3. To correct disturbances in water-electrolyte metabolism, Furosemide, Veroshpiron, intravenous saline, glucose, and calcium gluconate are prescribed.
4. Anabolic hormones and iron-containing drugs are indicated to accelerate the formation of red blood cells.
5. Immunomodulatory therapy - Levamisole.
6. Antihistamines - Zirtec, Cetrin, Suprastin.
7. A complex of vitamins and medications that improve metabolism.

Hyperbaric oxygen therapy has a positive effect on the severity of hematuria and kidney function. When renal failure progresses to the terminal stage, hemodialysis and a kidney transplant are required. Surgery is performed after the patient reaches the age of fifteen. There is no recurrence of the disease in the graft. In some cases, nephritis may develop.

Gene therapy for the syndrome is currently being actively developed. Its main goal is to prevent and slow down the deterioration of kidney function. This promising treatment option is now being introduced into medical practice Western medical laboratories.

Prognosis and prevention

Alport syndrome is a hereditary disease, the occurrence of which is simply impossible to prevent. Compliance with all doctor's orders and management healthy image life will help improve the general condition of patients.

The prognosis of the syndrome is considered favorable if patients have hematuria without proteinuria and hearing loss. Renal failure also does not develop in women without damage to the auditory analyzer. Even in the presence of persistent microhematuria, the disease practically does not progress in them and does not worsen the general condition of the patients.

Hereditary nephritis in combination with the rapid development of renal failure has an unfavorable prognosis in boys. They develop early dysfunction of the kidneys, eyes and ears. In the absence of timely and competent treatment, patients die at the age of 20-30 years.

Alport syndrome is a dangerous disease that, without qualified assistance, medical care worsens the quality of life of patients and ends in their death. To alleviate the course of hereditary nephritis, it is necessary to strictly follow all medical recommendations.

Video: lecture on Alport syndrome

– a hereditary kidney disease caused by a change in the synthesis of type IV collagen, which forms the basement membranes of the renal glomeruli, the structure of the inner ear, and the lens of the eye. Men suffer from an advanced form of the disease with severe symptoms. Women are often carriers of the gene, remaining healthy, or their symptoms of the disease are mild. The main symptoms are microhematuria, proteinuria, renal failure, sensory hearing loss, deformation and dislocation of the lens, cataracts. The diagnosis is established according to clinical and anamnestic data, the results of a general urinalysis, kidney biopsy, audiometry and ophthalmological examination. Treatment is symptomatic and includes therapy with ACE inhibitors and ARBs.

ICD-10

Q87.8 Other specified congenital anomaly syndromes not elsewhere classified

General information

Familial cases of hematuric nephropathy first came to the attention of researchers in 1902. Almost 30 years later, in 1927, the American doctor A. Alport discovered the frequent combination of hematuria with hearing loss and uremia in men, while in women the symptoms were absent or mild. He suggested the hereditary nature of the disease, which was later named Alport syndrome. Synonyms: hematuric nephritis, familial glomerulonephritis. The prevalence is low - 1 case per 5 thousand people. Pathology accounts for 1% of patients with renal failure, 2.3% of patients who have undergone kidney transplantation. The disease is diagnosed in people of all races, but the ratio various forms not the same.

Causes

By its nature, the syndrome is a heterogeneous hereditary disease - its development is provoked by a defect in the genes that encode the structure of various chains of type IV collagen. Genetic changes include deletions, splicing, missense and nonsense mutations. Their location determines the type of inheritance of the disease:

• X- linked dominant. Associated with a mutation in the COL4A5 locus, which is located on the sex chromosome X. The gene encodes the a5 chain of type 4 collagen. This genetic defect causes 80-85% of cases of hereditary nephritis. The disease is fully manifested in boys and men; in females, the remaining normal gene on the X chromosome compensates for the production of functional collagen.
• Autosomal recessive. Develops based on mutations in the C0L4A3 and COL4A4 genes. They are localized on the second chromosome and are responsible for the structure of the a3 and a4 chains of collagen. Patients with this variant of the syndrome account for about 15% of patients. The severity of symptoms does not depend on gender.
• Autosomal dominant. Nephritis occurs as a result of mutations in the COL4A3-COLA4 genes located on chromosome 2. As in the case of the autosomal recessive form of the disease, the synthesis of the a4 and a3 chains of type 4 collagen is disrupted. Prevalence – 1% of all cases of genetic nephritis.

Pathogenesis

The glomerular basement membrane has a complex structure; it is formed by a strict geometric sequence of type 4 collagen molecules and polysaccharide components. In Alport syndrome, there are mutations that cause a defective structure of helical collagen molecules. In the first stages of the disease, the basement membrane becomes thinner, begins to split and exfoliate. At the same time, thickened areas with uneven clearing appear. A fine granular substance accumulates inside. The progression of the disease is accompanied by complete destruction of the basal glomerular membrane of the glomerular capillaries, kidney tubules, structures of the inner ear and eyes. Thus, pathogenetically, Alport syndrome is represented by four links: a gene mutation, a defect in the structure of collagen, destruction of basement membranes, kidney pathology (sometimes hearing and vision impairment).

Symptoms

The most common manifestation of Alport syndrome is hematuria. Microscopically, this symptom is detected in 95% of women and 100% of men. During routine examination of boys, hematuria is detected already in the first years of life. Another common sign of the disease is proteinuria. Urinary protein excretion begins early in male patients with X-linked syndrome. childhood, for the rest - later. In girls and women, the level of protein excretion increases slightly; cases of severe proteinuria are extremely rare. All patients experience a steady progression of symptoms.

Patients often develop sensorineural hearing loss. Hearing impairment begins in childhood but becomes noticeable in adolescence or young adulthood. In children, hearing loss extends only to high-frequency sounds and is detected in specially created conditions - during audiometry. As the syndrome matures and progresses, the auditory perception of mid and low frequencies, including human speech, is impaired. With X-linked syndrome, hearing impairment is present in 50% of sick men by the age of 25, and in 90% by the age of 40. The severity of hearing loss is variable, ranging from changes in audiogram findings only to complete deafness. There are no pathologies of the vestibular apparatus.

Vision disorders include anterior lenticonus, a forward protrusion of the center of the eye's lens, and retinopathy. Both pathologies manifest as progressive deterioration visual function, redness, pain in the eyes. Some patients have stigmata of dysembryogenesis - anatomical abnormalities of the urinary system, eyes, ears, and limbs. There may be a high palate, shortening and curvature of the little fingers, fused toes, and widely spaced eyes.

Complications

Lack of treatment for patients with Alport syndrome leads to rapid progression of deafness and blindness, and the formation of cataracts. Some patients develop polyneuropathy - nerve damage, accompanied by muscle weakness, pain, cramps, tremor, paresthesia, and decreased sensitivity. Another complication is thrombocytopenia with a high risk of bleeding. The most dangerous condition for hereditary nephritis is end-stage renal failure. Men with a type of inheritance linked to the sex X chromosome are most susceptible to it. By the age of 60, 100% of patients in this group require hemodialysis, peritoneal dialysis, and donor kidney transplantation.

Diagnostics

Nephrologists, urologists, therapists and geneticists take part in the diagnostic process. The survey determines the age of onset of symptoms, the presence of hematuria, proteinuria, or deaths due to chronic renal failure in first-degree relatives. Alport syndrome is characterized by an early onset and a strong family history. Differential diagnosis is aimed at excluding the hematuric form of glomerulonephritis and secondary nephropathies. To confirm the diagnosis, the following procedures are performed:

1. Physical examination. Pallor is detected skin and mucous membranes, decreased muscle tone, external and somatic signs of dysembryogenesis - high palate, structural anomalies of the limbs, increased distance between the eyes and nipples. In the early stages of the disease, arterial hypotension is diagnosed, in the later stages - arterial hypertension.
2. General urine analysis. Red blood cells are detected and increased content protein – signs of hematuria and proteinuria. The urine protein indicator directly correlates with the severity of the syndrome; its change assesses the progression of the pathology, the likelihood of nephrotic syndrome, and chronic renal failure. There may be signs of abacterial leukocyturia.
3. Kidney biopsy examination. Microscopy visualizes a thinned basement membrane, splitting and separation of its layers. At a late stage, thickened dystrophic areas with “honeycombs” of clearing and zones of complete destruction of the layer are noted.
4. Molecular genetic research. Genetic diagnosis is not mandatory, but it allows you to make a more accurate prognosis and select the optimal treatment regimen. The structure of genes, mutations in which cause the development of the syndrome, is being studied. Most patients have mutations in the COL4A5 gene.
5. Audiometry, ophthalmological examination. Additionally, patients may be prescribed diagnostic consultations with an audiologist and an ophthalmologist. Audiometry reveals hearing loss: in childhood and adolescence - bilateral high-frequency hearing loss, in adulthood - low-frequency and mid-frequency hearing loss. The ophthalmologist determines the distortion of the shape of the lens, damage to the retina, the presence of cataracts, and decreased vision.

Treatment of Alport syndrome

There is no specific therapy. From an early age active symptomatic treatment, which reduces proteinuria. It helps prevent damage and atrophy of the renal tubules and the development of interstitial fibrosis. With the help of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, it is possible to stop the progression of the disease, achieve regression of glomerulosclerosis, tubulointerstitial and vascular changes in the kidneys. Patients with end-stage chronic renal failure are prescribed hemodialysis, peritoneal dialysis, and the question of the advisability of kidney transplantation is decided.

Prognosis and prevention

The syndrome is prognostically favorable in cases where hematuria occurs without proteinuria, there are no visual impairments or hearing loss. In addition, the prognosis is good for most women - even with hematuria, the disease progresses slowly and does not worsen the general condition. Due to the hereditary nature of the pathology, it is impossible to prevent its development. In families where the presence of an X-linked form of the syndrome has been established, prenatal diagnosis is possible. Genetic screening is especially recommended for women carrying boys.

Alport syndrome, or hereditary kidney inflammation, is a disease that is associated with a genetic predisposition. The disease occurs in both men and women, but, according to statistics, representatives of the stronger sex are more often susceptible to the pathological process. The disease itself is not accompanied by symptoms and is usually found in children aged three to eight years. As a rule, the diagnosis is made during a preventive examination and diagnostic examination of another disease. First, let's look at the provoking factors that lead to the emergence of a pathological process.

The true causes of the disease

The true causes of alport syndrome have not yet been fully studied by scientists. In our body there is a gene whose functional responsibility is the exchange of protein in kidney tissue. So the mutation of this gene is the most probable cause the appearance of the disease.

Now let's look at the provoking factors that can contribute to the onset of the disease. These include:

• severe infectious processes;
• vaccinations;
• strong physical activity.

As can be seen from numerous cases of medical practice, sometimes the development of alport syndrome can be facilitated by ordinary acute respiratory viral infection. It is in view of such high risks of morbidity that children who have a family history should undergo regular diagnostic examinations more often.

An interesting fact is that Alport syndrome has a dominant inheritance. What does it mean? This suggests that if a man is a carrier of a mutated gene, then his daughters will get sick, but his sons will be born healthy. At the same time, daughters will pass the disease on to all their children.

This disease was first recorded at the beginning of the last century. A physician was observing a family that had had hematuria for several generations. Later, an association was noted between hematuria and hearing loss, as well as ocular damage. Later, when medicine improved, doctors studied more deeply the genetic nature of this syndrome.

In most cases, its “owners” have relatives with kidney pathologies and other signs of this syndrome. Consanguineous marriages also play a role, as a result of which the child increases the likelihood of receiving the same genes. In patients with Alport syndrome, changes in the immune system are detected.

Symptoms

Hereditary nephritis has pronounced clinical symptoms. If speak about initial stages pathological process, it manifests itself as follows:

• the appearance of blood in the urine;
• deterioration of visual function;
• impaired hearing ability, up to the development of deafness.

Clinical symptoms will increase as the disease progresses. Over time, signs of intoxication appear, and anemia develops. The general condition and age of the patient affects the severity of the clinical picture.

Patients do not sleep well at night, so daytime they walk around drowsy

Other characteristic symptoms of the disease are:

• severe headaches;
• muscle pain;
• even small physical activity quickly tires the patient;
• dizziness;
• arterial hypertension, which is replaced by a sharp drop in pressure;
• dyspnea;
• shallow breathing;
• tinnitus that becomes permanent.

If we are talking about chronic form hereditary nephritis, the clinical picture here will be slightly different, namely:

• weakness and general malaise;
• frequent urge to urinate, blood;
• urination does not bring relief;
• nausea and vomiting;
• deterioration of appetite and, as a result, weight loss;
• hemorrhage;
• itchy skin;
• convulsions;
• pain in the chest;
• in severe cases, confusion and attacks of unconsciousness appear.

Symptoms of the disease are discovered purely by chance, during a preventive urine test for a viral disease or upon admission to kindergarten. At first, the general condition of the child is not changed, while the urinary syndrome is persistent and persistent.

Infectious processes of the respiratory tract, active physical activity, preventive vaccinations - all this can provoke increased hematuria. As for the presence of protein in the urine, proteinuria is initially unstable, and then gradually increases and becomes persistent.

Symptoms of intoxication also increase; hearing loss is especially observed in boys; children get tired quickly and suffer from severe headaches. Children are significantly behind in physical development.

Kinds

Experts distinguish three types of alport syndrome:

• pronounced symptoms and rapid progression of acute renal failure;
• the disease progresses rapidly, but there is no visual or hearing impairment;
• benign course of the disease, in which there are no clinical symptoms and progression. In this development scenario, the prognosis is favorable. If a woman has an autosomal recessive type of inheritance, then a more severe course of the disease is observed.

Diagnostic examination

If there is a suspicion of a hereditary factor in children, you should contact them as soon as possible. pediatrician. To clarify the diagnosis, laboratory and instrumental methods research. As for laboratory diagnostics, it includes general analysis blood and urine, as well as biochemical research.

If we talk about instrumental diagnostics, then this includes the following:

• ultrasound examination of the kidneys and adrenal glands;
• kidney biopsy;
• X-ray of the kidneys.

Sometimes additional genetic tests may be needed. Patients are prescribed a consultation with a nephrologist and additionally genetics.

Family history plays an important role in diagnosing the syndrome.

The main criteria for a diagnostic examination are:

• the presence of two people in the family with nephropathy;
• hematuria is the dominant symptom;
• hearing loss in a family member;
• the appearance of chronic renal failure in one of the relatives.

If we talk about differential analysis, then hereditary nephritis is compared with the acquired form of glomerulonephritis, in which hematuria is also observed. What's the difference? Glomerulonephritis has an acute onset and there is a direct connection with previous infection. If hereditary nephritis manifests itself as arterial hypotension, then glomerulonephritis, on the contrary, is expressed in arterial hypertension.

Fighting methods

Treatment of alport syndrome includes a combination of medications and special dietary nutrition. It is worth noting that specific medicines that would eliminate this particular genetic disease still does not exist. The focus of medications used for hereditary nephritis is associated with the normalization of kidney function. Dietary food for children is prescribed by a doctor individually. As a rule, such prescriptions must be followed for the rest of your life. Outdoor walks are shown. In extreme cases, the specialist may decide to carry out surgical intervention. Usually the operation is performed upon reaching the age of fifteen.

Proper nutrition

I would immediately like to note the foods that need to be excluded from the diet. These include:

• salty, fatty and smoked foods;
• spices and spicy foods;
• alcoholic drinks, but sometimes doctors may prescribe red wine for medicinal purposes;
• products that contain artificial colors.

Food should be fortified and high in calories, but not high in protein. Physical activity is excluded. Sports, especially for children, can only take place if they are not prohibited by a doctor.

Food must be complete and contain proteins, fats and carbohydrates in sufficient quantities, while the functional abilities of the kidneys must be taken into account.

Kidney failure is one of the most severe complications alport syndrome. According to statistics, insufficiency affects boys from sixteen to twenty years old. If there is no adequate treatment and the right way of life, then death occurs earlier than thirty years.

It is worth noting that the sanitization of chronic foci of infection plays an important role. For hematuria good effect provides herbal medicine, namely: yarrow, nettle, chokeberry. For chronic renal failure, hemodialysis and kidney transplantation are prescribed.

In addition, it is important to avoid contact with infectious patients to reduce the risk of developing respiratory diseases. Preventive vaccinations are contraindicated for children with hereditary nephritis, and vaccination can only be carried out according to epidemiological indications.

There is no prevention for alport syndrome. This is a genetic disease that cannot be prevented. If a child has been diagnosed with an illness, then you should adhere to the doctor’s recommendations and a proper lifestyle.

Kidney transplantation can completely eliminate the disease

If we talk about forecasts, the following criteria are extremely unfavorable:

• male gender;
• presence of chronic renal failure in family members;
• acoustic neuritis;
• the presence of protein in the urine.

Patients are prescribed medications that improve metabolism:

• vitamin A, E;
• pyridoxine;
• cocarboxylase.

Transplantation is the most effective treatment for alport syndrome. Recurrence of the disease in the graft is not observed, and only in minor cases can the development of nephritis occur.

So, alport syndrome is a serious illness that requires a timely and competent approach to treatment. There is no way to prevent hereditary nephritis, but its course can be alleviated by strictly following all medical recommendations.

Alport syndrome is a hereditary disease that manifests itself in the early development of renal failure, decreased hearing and visual acuity.

The disease is caused by genetic mutations affecting connective tissue - collagen type 4, which is part of many important structures of the body, including the kidneys, inner ear and eyes.

Alport syndrome is much more difficult for males. The fact is that the disease is most often transmitted through a mutated X chromosome. Since girls have two X chromosomes, the healthy one acts as a spare and facilitates the course of the disease.

In Alport syndrome, poisoning of the body occurs due to the inability of the kidneys to eliminate toxins. Therefore, in females, this pathology can cause infertility. And if pregnancy does occur, the toxins can kill both the child and the mother. Often Alport syndrome manifests itself during pregnancy, even if it has not made itself felt before.

Symptoms of the disease

As Wikipedia talks about such a disease as Alport syndrome, this hereditary disease characterized by hematuria (blood in the urine), leukocyturia (detection of white blood cells in a urine test), proteinuria (the presence of protein in the urine), deafness or hearing loss, sometimes cataracts and the development of kidney failure in adolescence. Sometimes kidney damage may appear only after 40-50 years.

The main symptom of the disease is the presence of blood in the urine, which indicates kidney disease. Sometimes it can only be detected microscopically, and in some cases the urine may turn pink, brown or red, especially against the background of associated infections, flu or viruses in the body. With age, in addition to hematuria, protein appears in the urine and the patient experiences arterial hypertension.

Although Alport syndrome is described by Wikipedia as a disease that manifests itself as cataracts, this is not always the case. Sometimes abnormal pigmentation of the retina can also occur, which significantly impairs vision. In addition, the cornea with such a hereditary disease is prone to the development of erosions. Therefore, they need to protect their eyes from foreign objects.

Alport syndrome is also characterized by hearing loss, which usually appears during adolescence. This problem can be solved with the help of a hearing aid.

Alport syndrome: treatment and prevention

Alport syndrome, the treatment of which is mainly symptomatic, requires mandatory sanitation of chronic foci of infections. Patients with this disease are contraindicated to receive vaccinations during times when there are no epidemics. There are also contraindications to taking glucocorticoid medications. For kidney failure, dialysis is used, and its development after 20 years of age is an indication for kidney transplantation.

Regarding the prevention of pathology, you should beware of urinary tract infections, which accelerate the development of renal failure. Women with Alport syndrome who decide to have a child must first consult with a geneticist who will help identify the carrier of the mutant gene. Although statistics show that about 20% of families experiencing Alport syndrome do not have relatives suffering from kidney failure. This fact proves that a mutated gene can arise spontaneously.

To protect your descendants from such a hereditary disease as Alport syndrome, it is necessary to avoid consanguineous marriages. And if a carrier of an abnormal gene is identified, in order to eradicate the pathology in the future, you can use donor genetic material and resort to the procedure of insemination or artificial insemination. In each individual case, individual consultation with specialists is necessary.

Alport syndrome (familial glomerulonephritis)- it's rare genetic disease, which is characterized by glomerulonephritis, progressive renal failure, sensorineural hearing loss and eye damage.

The disease was first described by British physician Arthur Alport in 1927.

Alport syndrome is very rare, but in the United States it is responsible for 3% of cases of end-stage renal disease in children and 0.2% in adults, and is considered the most common type of familial nephritis.

The type of inheritance of Alport syndrome can be different:

X-linked dominant (XLAS): 85%.
Autosomal recessive (ARAS): 15%.
Autosomal dominant (ADAS): 1%.

The most common X-linked form of Alport syndrome results in end-stage renal failure in men. Hematuria usually occurs in boys with Alport syndrome in the first years of life. Proteinuria is usually absent in childhood, but the condition often develops in males with XLAS and in both sexes with ARAS. Hearing loss and eye damage are never detected at birth but occur in late childhood or adolescence, shortly before kidney failure develops.

Causes and mechanism of development of Alport syndrome

Alport syndrome is caused by mutations in the COL4A4, COL4A3, COL4A5 genes, which are responsible for collagen biosynthesis. Mutations in these genes disrupt the normal synthesis of type IV collagen, which is a very important structural component of the basement membranes in the kidneys, inner ear and eyes.

Basement membranes are thin film-like structures that support tissues and separate them from each other. When type IV collagen synthesis is impaired, the glomerular basement membranes in the kidneys are unable to properly filter toxic products from the blood, allowing proteins (proteinuria) and red blood cells (hematuria) to pass into the urine. Abnormalities in type IV collagen synthesis lead to renal failure and kidney failure, which is main reason death due to Alport syndrome.

Clinic

Hematuria is the most common and early manifestation of Alport syndrome. Microscopic hematuria is observed in 95% of women and almost all men. In boys, hematuria is usually detected in the first years of life. If hematuria is not detected in a boy during the first 10 years of life, then American experts recommend that he is unlikely to have Alport syndrome.

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria usually progresses. Significant proteinuria is uncommon in female patients.

Hypertension is more often present in male patients with XLAS and in patients of both sexes with ARAS. The incidence and severity of hypertension increases with age and as renal failure progresses.

Sensorineural hearing loss (hearing impairment) is a characteristic manifestation of Alport syndrome, which is observed quite often, but not always. There are entire families with Alport syndrome who suffer from severe nephropathy but have normal hearing. Hearing loss is never detected at birth. Bilateral high-frequency sensorineural hearing loss usually appears in the first years of life or early adolescence. At an early stage of the disease, hearing loss is determined only by audiometry.

As it progresses, hearing loss extends to low frequencies, including human speech. Once hearing loss occurs, renal involvement should be expected. American scientists claim that with X-linked Alport syndrome, 50% of men suffer from sensorineural hearing loss by the age of 25, and by the age of 40 - about 90%.

Anterior lenticonus (bulging forward of the central portion of the lens of the eye) occurs in 25% of patients with XLAS. Lenticonus is not present at birth, but over the years it leads to progressive deterioration of vision, which forces patients to change glasses frequently. The condition is not accompanied by eye pain, redness, or color vision problems.

Retinopathy is the most common visual manifestation of Alport syndrome, affecting 85% of men with the X-linked form of the disease. The onset of retinopathy usually precedes renal failure.

Posterior polymorphic corneal dystrophy is a rare condition in Alport syndrome. Most have no complaints. The L1649R mutation in the collagen gene COL4A5 may also cause retinal thinning, which is associated with X-linked Alport syndrome.

Diffuse leiomyomatosis of the esophagus and bronchial tree is another rare condition that occurs in some families with Alport syndrome. Symptoms appear in late childhood and include difficulty swallowing (dysphagia), vomiting, epigastric and chest pain, frequent bronchitis, shortness of breath, cough. Leiomyomatosis confirmed computed tomography or MRI.

Autosomal recessive form of Alport syndrome

ARAS accounts for only 10-15% of cases of the disease. This form occurs in children whose parents are carriers of one of the affected genes, the combination of which causes the disease in the child. The parents themselves have no or mild symptoms, but the children are seriously ill - their symptoms resemble XLAS.

Autosomal dominant form of Alport syndrome

ADAS is the rarest form of the syndrome and affects one generation after another, with men and women equally severely affected. Renal manifestations and deafness resemble XLAS, but renal failure may occur later in life. Clinical manifestations ADAS are complemented by a tendency to bleeding, macrothrombocytopenia, Epstein syndrome, and the presence of neutrophilic inclusions in the blood.

Diagnosis of Alport syndrome

Lab tests. Urinalysis: Patients with Alport syndrome most often have blood in the urine (hematuria), as well as high content protein (proteinuria). Blood tests show kidney failure.
Tissue biopsy. The kidney tissue obtained from the biopsy is examined using electron microscopy for the presence of ultrastructural abnormalities. A skin biopsy is less invasive and is recommended by US experts to be performed first.
Genetic analysis. In diagnosing Alport syndrome, if doubt remains after a kidney biopsy, genetic analysis used to obtain a definite answer. Mutations of type IV collagen synthesis genes are determined.
Audiometry. All children with a family history suggestive of Alport syndrome should undergo high-frequency audiometry to confirm sensorineural hearing loss. Periodic monitoring is recommended.
Eye examination. An examination by an ophthalmologist is very important for early detection and monitoring of anterior lenticonus and other abnormalities.
Ultrasound of the kidneys. On late stages Alport syndrome, ultrasound examination of the kidneys helps identify structural abnormalities.

British experts, based on new data (2011) on genetic mutations In patients with X-linked Alport syndrome, testing for COL4A5 mutations is recommended if the patient meets at least two Gregory diagnostic criteria, and testing for COL4A3 and COL4A4 if the COL4A5 mutation is not detected or autosomal inheritance is suspected.

Treatment of Alport syndrome

Alport syndrome is not yet curable. Studies have shown that ACE inhibitors can reduce proteinuria and slow the progression of kidney failure. Thus, the use of ACE inhibitors is advisable in patients with proteinuria, regardless of the presence of hypertension. The same applies to ATII receptor antagonists. Both classes of drugs appear to help reduce proteinuria by reducing intraglomerular pressure. Moreover, inhibition of angiotensin II, a growth factor responsible for glomerular sclerosis, could theoretically slow down sclerosis.

Some researchers suggest that cyclosporine may reduce proteinuria and stabilize renal function in patients with Alport syndrome (studies have been small). But reports suggest that patients' response to cyclosporine is highly variable, and the drug can sometimes accelerate interstitial fibrosis.

For renal failure, standard therapy includes erythropoietin to treat chronic anemia, drugs to control osteodystrophy, correction of acidosis, and antihypertensive therapy to control blood pressure. Hemodialysis and peritoneal dialysis are used. Kidney transplantation is not contraindicated for patients with Alport syndrome: transplant experience in the United States has shown good results.

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is now being actively studied by Western medical laboratories.

Konstantin Mokanov

This syndrome was first described by the English doctor Arthur Alport in 1927, who observed an entire family with widespread renal failure and simultaneous damage to the organs of vision and hearing in several generations.

Subsequently, conclusions were drawn about genetic origin diseases, which was ultimately proven in practice.

What it is?

Alport syndrome is a rare genetic disease associated with a disorder in the structure of the fibrillar protein collagen, which is part of the human kidneys, organs of vision and hearing.

Due to the pathology, the patient develops renal failure, hearing deteriorates and visual acuity decreases. The disease is characterized by constant progress.

In medical practice, this syndrome has other names - hereditary nephritis or familial glomerulonephritis. The disease is hereditary and is associated with a pathology in one of the genes that is responsible for the structure of the collagen protein.

This connection serves as an integral part of the cochlear apparatus of the hearing organs, the lenses of the eyes and the glomerular apparatus of the kidneys. Due to this, the patient simultaneously develops a number of symptoms in the relevant organs: kidney failure, deterioration of vision and hearing.

According to international classification according to ICD-10 it has code Q87.8(“Other Congenital Anomaly Syndromes”). That is, the disease refers to congenital pathologies with chromosomal abnormalities.

According to statistics, the number of people with this anomaly in genes is about 0.017% throughout the planet, in countries North America the figure is several times higher. It has been noticed that the mutated gene is more often activated in males.

Classification of the disease

Highlight 3 main shapes diseases:

1. Dominant type of inheritance associated with the X chromosome. Thinning and splitting of the basement membrane in the kidneys, consisting of collagen, develops. Symptoms: hearing loss, decreased vision, nephritis and hematuria. Constantly evolving.
2. Autosomal recessive type of inheritance. The clinical picture is similar to the previous type, but without hearing impairment.
3. Autosomal dominant type of inheritance. Called benign familial hematuria. Renal failure does not develop, the course of the disease is favorable.

Causes

The main reason is a mutation of the genes responsible for the code of collagen chains.

This pathology is usually transmitted from parents to, in rare cases it occurs independently (20% of cases). Moreover, the mother passes the X chromosome to her son and daughter, but the father can only pass it on to the daughter.

Probability of developing the disease increases many times over if close relatives had other chronic diseases genitourinary system. It has also been noted that the disease can be triggered by additional factors:

• infectious diseases (viral, bacterial and fungal);
• injuries;
• taking medications;
• vaccinations;
• increased mental and physical stress;
• stress and emotional fatigue.

Symptoms of the disease

The first symptoms appear aged 3-6 years. Gene mutation leads to collagen deficiency, which in turn negatively affects the condition of the basement membrane in the kidneys, eye lenses and the structure of the inner ear. The functionality of these organs decreases.

The kidneys are the first to suffer - their filtration ability deteriorates, as a result of which proteins, toxins and red blood cells begin to enter the blood. Constantly progressive renal failure develops.

At the same time and with a delay, a decrease in visual acuity and deterioration of hearing occur. Symptoms tend to constantly strengthen and progress. Your child may experience additional symptoms:

• blood in urine;
• increased levels in blood and urine;
• anemia;
• symptoms of intoxication (nausea, vomiting, weakness);
• muscle pain;
• blood pressure surges;
• decreased physical activity;
• headache;
• insomnia;
• increased body temperature;
• chills;
• developmental delay from peers;
• hearing loss (inability to distinguish between low and high tones);
• lens abnormalities.

In the future, without adequate treatment, the disease may acquire a chronic form, which is characterized by:

• chronic fatigue;
• constant malaise;
• dry skin;
• decreased appetite;
• weight loss;
• unpleasant taste in the mouth;
• mental retardation and lethargy;
• constant thirst and dry mouth;
• pale skin color.

Diagnostic measures

First of all, the doctor studies the medical history of the parents, since the disease is transmitted from parents to children in 4 cases out of 5. He pays attention to the following details in the child and parents:

• presence of hematuria;
• a kidney biopsy showed abnormalities in the structure of the basement membrane;
• congenital problems with vision and hearing;
• there were cases of renal failure with a fatal outcome in the family;
• There is a constant decrease in hearing and vision in the child.

Enough presence of 3 signs to almost certainly make a diagnosis. Next will be appointed additional research as:

• kidney,
• biopsy of collagen structures,
• radiography,
• urine and blood,
• consultations with a geneticist and nephrologist.

How to treat pathology?

To date, the disease cannot be completely cured.

Complex of therapeutic measures helps stop the progression of the disease. For this purpose, medications and special nutrition are used, and there is no specific medicine against this disease.

To slow down the development of renal failure, angiotensin-converting enzyme (ATP) inhibitors and angiotensin blockers are prescribed. This reduces proteinuria (protein levels in the urine) and normalizes kidney function.

Among the additional medical supplies Erythropoietin can be used in the presence of anemia and drugs to normalize blood pressure. Peritoneal dialysis is also possible. In severe cases, the patient kidney transplant needed regardless of age.

As adjuvant therapy It is important for children to follow a number of rules:

1. reduce physical activity (up to and including exemption from physical education lessons);
2. take vitamins A, B6 and E to normalize metabolic processes in the body;
3. take walks in the fresh air;
4. engage in herbal medicine to improve kidney function and cleanse the blood (use decoctions and infusions of yarrow, nettle and chokeberry juice).

It is worth considering separately nutrition, which directly affects the kidneys and can both help and harm. The patient is prohibited from eating fatty, fried, salty, smoked and spicy foods. These types of foods overload the kidneys and can cause the disease to progress.

You should also not drink alcohol, with the exception of red wine in small quantities and only as directed by a doctor. Any products containing dyes (colored soda, jelly products with dye, etc.) are hazardous to health.

All food must be nutritious and contain as many vitamins as possible. At the same time, food should be well digested and not overload digestive system, which affects kidney function. Lean meats (veal, lean beef), fish, seafood, poultry, as well as various vegetables and fruits are suitable for this.

Forecast

The prognosis depends on the form of the disease and the gender of the person. In the male line, the syndrome develops according to a similar scenario, so data from the father’s medical history can help predict the course of the disease in the son; such a dependence is not observed.

The most dangerous is an X-dominant form, progressing quite quickly and posing a threat to life due to chronic renal failure. However, it is difficult to make an accurate forecast.

Unlike the X-dominant form, the autosomal dominant type is less aggressive and renal failure is less severe. It is possible to slow the development of symptoms almost completely. The prognosis is favorable in most cases. The patient only needs constant monitoring of the condition of the kidneys and compliance. Drug therapy usually not used.

Alport syndrome cannot be avoided as it is a genetic disorder. There are no effective preventive measures. There are also no specific drugs against the disease. The main thing is to monitor the patient’s condition.

If a disease is detected, it is necessary to undergo all examinations and follow the recommendations of doctors.

The only truly effective way is kidney transplant, which is carried out in case of serious renal failure and a threat to the patient’s life.

Find out how a kidney transplant operation is performed in the video:

Alport syndrome (hereditary nephritis) is rare. This pathology provokes visual impairment and hearing loss. This often leads to the need for a kidney transplant.

This syndrome appears at 3–5 years of age. Hereditary nephritis in children is constantly progressing. At the same time, the child loses hearing and vision, and the glomerular apparatus of the kidneys is affected.

Alport syndrome develops due to a mutation in the gene that produces collagen. This type of collagen is involved in the construction of the lens capsule and part of the inner ear. Hence, their function is impaired, and the functions of the kidneys themselves are also impaired.

According to the international classification, this pathology refers to congenital anomalies, chromosomal disorders and deformations. She is considered congenital defect, since several organs and systems suffer at once.

Causes of pathological changes

The main cause of Alport syndrome is a gene mutation.

The affected gene is in most cases transmitted from one of the parents. If someone in your family suffered from a disease of the urinary system, the likelihood of pathology increases significantly.

In 20% of all cases, spontaneous gene mutation occurs. This means that completely healthy parents are guaranteed to have a child with a similar pathology.

Symptoms

Collagen is the most important component of connective tissue. Its deficiency provokes changes in the basement membranes of the renal glomeruli, the ocular apparatus and the inner ear. These organs cease to cope with their functions.

Symptoms of this pathology are divided into two main types:

• renal (blood and urine);
• non-renal.

Renal manifestations are also called isolated urinary syndrome.

It does not appear immediately after birth, but closer to 3–5 years. There are cases where the pathology was detected much later at the age of 7–9 years. But there are always tiny drops of blood in the urine. At first, simply sick people may not notice them ().

With this pathology, it is important to make a correct diagnosis in time, remove physical activity, provide a strict diet, regular complex treatment. Plays a big role correct image life. Parents should not panic, because modern medicine is able to help even with such a genetic disorder as Alport syndrome. The disease is inherited, so it is necessary to take therapeutic measures against all family members who develop symptoms.

Alport syndrome is a hereditary disease that is directly characterized by a consistent decrease in kidney function, coupled with pathology of hearing and even vision. Currently, in our country, this type of illness among the (mainly) child population is approximately 17:100,000.

Main reasons

According to experts, Alport syndrome occurs due to abnormalities in a gene that is located in the long arm of the X chromosome in the so-called zone 21-22q. In addition, disruption of the integral structure of the so-called type 4 collagen is also the cause of this disease. In science, collagen is understood as a protein that is a direct component of connective tissue, ensuring its elasticity and continuity.

Symptoms

Alport syndrome usually first appears in children aged five to ten years and manifests itself in the form of hematuria (blood in the urine). Most often, this diagnosis is discovered by chance, that is, during the next examination by a specialist. In addition, Alport syndrome also manifests itself in the form of so-called stigmas of dysembryogenesis. These are relatively minor deviations that do not play a special role in the functioning of the main systems of the body. Doctors note the epicanthus (a small fold at the inner corner of the eye), high palate, slight deformation of both ears and other signs. Consistency is also a sure sign of this disease, and hearing loss is much more often diagnosed in boys. All of the above symptoms are most often detected in adolescence, while the common chronic one makes itself felt only during adulthood.

Diagnosis

Alport syndrome in children is usually diagnosed based on evidence of the presence of this type of illness in other family members. For example, to confirm the disease, it is enough to meet three of the five criteria listed below:

• hearing loss;
• cases of death from chronic renal failure of close relatives;
• confirmation of hematuria in family members;
• vision pathologies;
• the presence of specific changes during kidney biopsy.

In the absence of specific therapy, doctors must first slow the progression of kidney failure. With a diagnosis such as Alport's disease, children are strictly prohibited from physical activity; they are prescribed. Important attention is paid to the sanitation of so-called infectious foci. The use of cytostatics and various types of hormonal drugs in treatment helps to improve the condition. However, it is most often prescribed as the preferred method of treatment. It should be noted that when hematuria is detected without significant hearing impairment, the overall prognosis for the course of the disease is somewhat more favorable. In this kind of situation, renal failure is diagnosed extremely rarely.

Alport syndrome is a hereditary disease characterized by a progressive decline in kidney function in combination with hearing and vision pathologies. In Russia, the incidence of the disease among children is 17:100,000.

Causes of Alport syndrome

It has been established that a gene located in the long arm of the X chromosome in the 21-22 q zone is responsible for the development of the disease. The cause of the disease is a violation of the structure of type IV collagen. Collagen is a protein, the main component of connective tissue, which provides its strength and elasticity. In the kidneys, a defect in the collagen of the vascular wall is detected, in the area of ​​the inner ear - in the organ of Corti, in the eye - in the lens capsule.

Symptoms of Alport syndrome

With Alport syndrome, there is significant variability in external manifestations. As a rule, the disease manifests itself at the age of 5-10 years with hematuria (the appearance of blood in the urine). Hematuria is usually detected incidentally during examination of a child. Hematuria can occur with or without proteinuria (the appearance of protein in the urine). With a pronounced loss of protein, nephrotic syndrome can develop, which is characterized by edema, increased blood pressure, symptoms of poisoning of the body with harmful products and decreased kidney function. It is possible to increase the number of leukocytes in the urine in the absence of bacteria.

In most patients, the stigma of dysembryogenesis attracts attention. Stigmas of dysembryogenesis are small external deviations that do not significantly affect the functioning of the body. These include: epicanthus (the fold at the inner corner of the eye), deformation of the ears, high palate, an increase in the number of fingers or their fusion.

Epicanthus. Syndactyly.

Very often, the same stigmas of disembryogenesis are detected in sick family members.

Hearing loss as a result of acoustic neuritis is also characteristic of Alport syndrome. Hearing loss develops more often in boys and is sometimes detected earlier than kidney damage.

Visual anomalies manifest themselves in the form of lenticonus (change in the shape of the lens), spherophakia (spherical shape of the lens) and cataracts (clouding of the cornea).

Symptoms of kidney disease usually appear during adolescence. Chronic renal failure is diagnosed in adulthood. Sometimes rapid progression of the disease is possible with the formation of end-stage renal failure in childhood.

Diagnosis of Alport syndrome

Alport syndrome can be assumed based on pedigree data based on the presence of the disease in other family members. To diagnose the disease, it is necessary to identify three of five criteria:

Presence of hematuria or mortality from chronic renal failure in the family;
presence of hematuria and/or proteinuria in family members;
identification of specific changes in kidney biopsy;
hearing loss;
congenital pathology vision.

Treatment of Alport syndrome

In the absence of specific treatment, the main goal is to slow the progression of renal failure. Children are prohibited from physical activity and are prescribed a well-balanced diet. Special attention is given to the sanitation of infectious foci. The use of hormonal drugs and cytostatics does not lead to a significant improvement in the condition. The main method of treatment remains kidney transplantation.

An unfavorable prognosis for the course of the disease, which is characterized by the rapid development of end-stage renal failure, is most likely if the following criteria are present:

Male gender;
- high concentration of protein in urine;
- early development of renal dysfunction in family members;
- hearing loss.

If isolated hematuria without proteinuria and hearing impairment is detected, the prognosis for the course of the disease is favorable, renal failure does not develop.

General practitioner, nephrologist Sirotkina E.V.

Alport syndrome or hereditary nephritis is a kidney disease that is inherited. In other words, the disease affects only those who have a genetic predisposition. Men are most susceptible to the disease, but the disease also occurs in women. The first symptoms appear in children between 3 and 8 years of age. The disease itself may be asymptomatic. Most often it is diagnosed during a routine examination or during the diagnosis of another underlying disease.

Etiology

The etiology of hereditary nephritis still cannot be fully established. The most likely cause is considered to be a mutation of the gene that is responsible for the synthesis of proteins in the kidney tissue.

The following factors can contribute to the development of the pathological process:

• severe infectious diseases;
• excessive physical activity;
• vaccinations.

In medical practice, there have been cases when the development of hereditary nephritis could be provoked even by ordinary ones. Therefore, children who have a genetic predisposition should undergo full examination more often.

It is noteworthy that hereditary nephritis has a dominant type of inheritance. This means that if the carrier is a man, then only his son will be born healthy. The daughter will not only be a carrier of the gene, but will also pass it on to both sons and daughters.

General symptoms

The clinical picture of Alport syndrome has well-defined symptoms. At the initial stages of development, the following is observed:

• decreased vision;
• hearing impairment (in some cases, up to deafness in one ear);
• blood in urine.

As hereditary nephritis develops, the signs of the disease become more pronounced. There is severe intoxication of the body and... The latter occurs due to a significant and sharp decrease in red cells in the blood. Characteristic symptoms of Alport syndrome:

• headache and muscle pain;
• rapid fatigue even with minor physical exertion;
• dizziness;
• unstable blood pressure;
• shallow breathing, shortness of breath;
• constant ringing in the ears;
• disturbance of biological rhythm (especially in children).

Insomnia at night and drowsiness during the day most often affects children and the elderly. The severity of symptoms also depends on the general condition of the patient and his age.

In the chronic form of the disease, the following clinical picture is observed:

• general malaise and weakness;
• frequent urination that does not bring relief (possibly with blood);
• nausea and vomiting;
• lack of appetite and, as a result, weight loss;
• bruising;
• itching of the skin;
• chest pain;
• convulsions.

In some cases, when chronic stage Alport syndrome, the patient experiences confusion and seizures of unconsciousness. In children, such signs are diagnosed very rarely.

Forms of disease development

In official medicine, it is customary to distinguish three forms of the disease:

• the first - rapidly progresses to renal failure, the symptoms are well expressed;
• second - the course of the disease is progressive, but hearing loss and visual impairment are not observed;
• the third is a benign course. There are no symptoms or progressive nature of the disease.

Diagnostics

First of all, when diagnosing Alport syndrome, family history is taken into account.

If you suspect hereditary nephritis in children, you should immediately contact your pediatrician. The study uses both laboratory and instrumental tests. After a personal examination and medical history, the doctor may prescribe the following laboratory tests:

The standard program of instrumental research includes the following:

• kidney x-ray;
• kidney biopsy.

In some cases, the doctor may prescribe special genetic tests. Additionally, you may need to consult a medical geneticist and nephrologist.

Treatment

Drug treatment of Alport syndrome is combined with diet. It is worth noting that there are no specific drugs aimed specifically at eliminating this genetic disease. All medications are aimed at normalizing kidney function.

For children, the diet is prescribed strictly individually. In most cases, the patient needs to adhere to this diet for the rest of his life.

In some cases, surgical intervention is necessary. For children, such operations are performed only when they reach 15–18 years of age. Kidney transplantation can completely eliminate the disease.

Diet

The following foods should not be present in the patient’s diet:

• too salty, fatty, smoked;
• spicy, spicy dishes;
• products with artificial colors.

Alcohol is almost completely excluded. According to the doctor's recommendation, the patient can drink red wine.

The diet must contain the required amount of vitamins and minerals. Food should be high in calories and not high in protein.

Physical activity is excluded. Sports should only be performed as prescribed by a doctor. Especially, the latter circumstance concerns children.

Possible complications

The most serious complication is. As shown medical practice, in most cases, boys aged 16–20 years suffer from deficiency. Without treatment and proper lifestyle, death occurs before age 30.

Prevention

There is no prevention for hereditary nephritis. This genetic disease cannot be prevented. If a child is diagnosed with an illness, then you should strictly adhere to all the recommendations of a competent doctor and lead a correct lifestyle. The most effective treatment method today is organ transplantation.

Alport syndrome (familial glomerulonephritis) is a rare genetic disease characterized by glomerulonephritis, progressive renal failure, sensorineural hearing loss and eye damage.

The disease was first described by British physician Arthur Alport in 1927.

Alport syndrome is very rare, but in the United States it is responsible for 3% of cases of end-stage renal disease in children and 0.2% in adults, and is considered the most common type of familial nephritis.

The type of inheritance of Alport syndrome can be different:

X-linked dominant (XLAS): 85%.
Autosomal recessive (ARAS): 15%.
Autosomal dominant (ADAS): 1%.

The most common X-linked form of Alport syndrome results in end-stage renal failure in men. Hematuria usually occurs in boys with Alport syndrome in the first years of life. Proteinuria is usually absent in childhood, but the condition often develops in males with XLAS and in both sexes with ARAS. Hearing loss and eye damage are never detected at birth but occur in late childhood or adolescence, shortly before kidney failure develops.

Causes and mechanism of development of Alport syndrome

Alport syndrome is caused by mutations in the COL4A4, COL4A3, COL4A5 genes, which are responsible for collagen biosynthesis. Mutations in these genes disrupt the normal synthesis of type IV collagen, which is a very important structural component of the basement membranes in the kidneys, inner ear and eyes.

Basement membranes are thin film-like structures that support tissues and separate them from each other. When type IV collagen synthesis is impaired, the glomerular basement membranes in the kidneys are unable to properly filter toxic products from the blood, allowing proteins (proteinuria) and red blood cells (hematuria) to pass into the urine. Abnormalities in the synthesis of type IV collagen lead to renal failure and kidney failure, which is the main cause of death in Alport syndrome.

Clinic

Hematuria is the most common and early manifestation of Alport syndrome. Microscopic hematuria is observed in 95% of women and almost all men. In boys, hematuria is usually detected in the first years of life. If hematuria is not detected in a boy during the first 10 years of life, then American experts recommend that he is unlikely to have Alport syndrome.

Proteinuria is usually absent in childhood, but sometimes develops in boys with X-linked Alport syndrome. Proteinuria usually progresses. Significant proteinuria is uncommon in female patients.

Hypertension is more often present in male patients with XLAS and in patients of both sexes with ARAS. The incidence and severity of hypertension increases with age and as renal failure progresses.

Sensorineural hearing loss (hearing impairment) is a characteristic manifestation of Alport syndrome, which is observed quite often, but not always. There are entire families with Alport syndrome who suffer from severe nephropathy but have normal hearing. Hearing loss is never detected at birth. Bilateral high-frequency sensorineural hearing loss usually appears in the first years of life or early adolescence. At an early stage of the disease, hearing loss is determined only by audiometry.

As it progresses, hearing loss extends to low frequencies, including human speech. Once hearing loss occurs, renal involvement should be expected. American scientists claim that with X-linked Alport syndrome, 50% of men suffer from sensorineural hearing loss by the age of 25, and by the age of 40 - about 90%.

Anterior lenticonus (bulging forward of the central portion of the lens of the eye) occurs in 25% of patients with XLAS. Lenticonus is not present at birth, but over the years it leads to progressive deterioration of vision, which forces patients to change glasses frequently. The condition is not accompanied by eye pain, redness, or color vision problems.

Retinopathy is the most common visual manifestation of Alport syndrome, affecting 85% of men with the X-linked form of the disease. The onset of retinopathy usually precedes renal failure.

Posterior polymorphic corneal dystrophy is a rare condition in Alport syndrome. Most have no complaints. The L1649R mutation in the collagen gene COL4A5 may also cause retinal thinning, which is associated with X-linked Alport syndrome.

Diffuse leiomyomatosis of the esophagus and bronchial tree is another rare condition that occurs in some families with Alport syndrome. Symptoms appear in late childhood and include difficulty swallowing (dysphagia), vomiting, epigastric and chest pain, frequent bronchitis, shortness of breath, and cough. Leiomyomatosis is confirmed by computed tomography or MRI.

Autosomal recessive form of Alport syndrome

ARAS accounts for only 10-15% of cases of the disease. This form occurs in children whose parents are carriers of one of the affected genes, the combination of which causes the disease in the child. The parents themselves have no or mild symptoms, but the children are seriously ill - their symptoms resemble XLAS.

Autosomal dominant form of Alport syndrome

ADAS is the rarest form of the syndrome and affects one generation after another, with men and women equally severely affected. Renal manifestations and deafness resemble XLAS, but renal failure may occur later in life. Clinical manifestations of ADAS are complemented by a tendency to bleeding, macrothrombocytopenia, Epstein syndrome, and the presence of neutrophilic inclusions in the blood.

Diagnosis of Alport syndrome

Lab tests. Urinalysis: Patients with Alport syndrome most often have blood in the urine (hematuria) as well as high levels of protein (proteinuria). Blood tests show kidney failure.
Tissue biopsy. The kidney tissue obtained from the biopsy is examined using electron microscopy for the presence of ultrastructural abnormalities. A skin biopsy is less invasive and is recommended by US experts to be performed first.
Genetic analysis. In diagnosing Alport syndrome, if doubt remains after a kidney biopsy, genetic testing is used to obtain a definitive answer. Mutations of type IV collagen synthesis genes are determined.
Audiometry. All children with a family history suggestive of Alport syndrome should undergo high-frequency audiometry to confirm sensorineural hearing loss. Periodic monitoring is recommended.
Eye examination. An examination by an ophthalmologist is very important for early detection and monitoring of anterior lenticonus and other abnormalities.
Ultrasound of the kidneys. In the later stages of Alport syndrome, ultrasound examination of the kidneys can help identify structural abnormalities.

British experts, based on new data (2011) on genetic mutations in patients with X-linked Alport syndrome, recommend analysis for mutations of the COL4A5 gene if the patient meets at least two diagnostic criteria according to Gregory, and analysis of COL4A3 and COL4A4 if the COL4A5 mutation is not autosomal inheritance is detected or suspected.

Treatment of Alport syndrome

Alport syndrome is not yet curable. Studies have shown that ACE inhibitors can reduce proteinuria and slow the progression of kidney failure. Thus, the use of ACE inhibitors is advisable in patients with proteinuria, regardless of the presence of hypertension. The same applies to ATII receptor antagonists. Both classes of drugs appear to help reduce proteinuria by reducing intraglomerular pressure. Moreover, inhibition of angiotensin II, a growth factor responsible for glomerular sclerosis, could theoretically slow down sclerosis.

Some researchers suggest that cyclosporine may reduce proteinuria and stabilize renal function in patients with Alport syndrome (studies have been small). But reports suggest that patients' response to cyclosporine is highly variable, and the drug can sometimes accelerate interstitial fibrosis.

For renal failure, standard therapy includes erythropoietin to treat chronic anemia, drugs to control osteodystrophy, correction of acidosis, and antihypertensive therapy to control blood pressure. Hemodialysis and peritoneal dialysis are used. Kidney transplantation is not contraindicated for patients with Alport syndrome: transplant experience in the United States has shown good results.

Gene therapy for various forms of Alport syndrome is a promising treatment option, which is now being actively studied by Western medical laboratories.

Konstantin Mokanov

Alport syndrome (AS) is an inherited type IV collagen disorder characterized by the combination of progressive hematuric nephritis with ultrastructural changes and sensorineural hearing loss. Visual disturbances are also common with this syndrome. Microhematuria, detected early in life, is a constant characteristic sign of the disease.

Recurrent episodes of gross hematuria occur in approximately 60% of patients under the age of 16 years, but are quite rare in adults. Over time, the disease develops and progresses with age, depending on the gender of the patient and the type of inheritance of the disease. is a late sign.

Bilateral sensorineural hearing loss, affecting high- and mid-frequency hearing, is progressive in children but may become apparent later. There are reports of several types of visual disorders also progressing with age. Anterior lenticone is a cone-shaped protrusion of the front part of the lens. Yellowish spots appear on the retina of the eye, which are asymptomatic. Both types of lesions are specific and are observed in approximately one third of patients. There are also reports of recurrent corneal erosions in patients with AS.

Morphology

By light microscopy, renal tissue obtained from early stages of CA appears normal. Focal and segmental thickening of the capillary walls of the glomeruli, better identified by silver staining, become visible as the disease progresses. They are combined with nonspecific tubular lesions and interstitial fibrosis. Standard immunofluorescence is usually negative. However, weak and/or focal deposits of classes G and M and/or complement fraction S3 may be detected. The main damage is detected by the ultrastructural method. They are characterized by thickening (up to 800-1200 nm) with splitting and fragmentation of the lamina densa into several fibers forming a network like a basket. The changes may be fragmented (heterogeneous), alternating with areas of normal or reduced thickness. In general, the most prominent feature in children is an uneven alternation of very thick and very thin areas of the GBM. Diffuse thinning of the GBM is found in approximately 20% of patients with SA.

At the genetic level, SA is a heterogeneous disease: mutations of COL4A5 on the X chromosome are associated with X-linked SA, while mutations of COL4A3 or COL4A4 on chromosome 2 are associated with autosomal forms of the disease.

X-linked Alport syndrome.

Clinical symptoms.

The X-linked variant is the most common form of SA, characterized by a more severe course of the disease in male patients than in female patients, and the absence of transmission in the male line. Availability hematuria– a necessary criterion for diagnosis. gradually increases with age and can subsequently lead to the development of nephrotic syndrome. All male patients progress to end-stage renal disease. There are two types of SA - juvenile, in which ESRD develops around the age of 20 years in men with maternal transmission of the disease, and adult, characterized by a more variable course and development of ESRD around the age of 40 years. In heterozygous females, hematuria is detected only in adulthood. It is absent in less than 10% of women (carriers). The risk of developing ESRD in women under 40 years of age is about 10-12% (versus 90% in men), but increases after 60 years of age. Most heterozygotes never develop ESRD. Bilateral sensorineural hearing loss progresses in most male and some female patients. Changes in the organ of vision, anterior lenticonus and/or perimacular spots are observed in 1/3 of patients. In families with AS, women may experience diffuse esophageal leiomyomatosis, which also includes damage to the tracheobronchial tree and female genital tract and sometimes congenital cataracts.

Molecular genetics made it possible to establish the characteristics of mutations in the COL4A5 gene. They cause differences in clinical manifestations, course and prognosis.

Autosomal recessive Alport syndrome

Alport syndrome is inherited in an autosomal recessive manner in approximately 15% of affected European families. This type of inheritance is more common in countries with higher rates of consanguineous marriage. Clinical symptoms and ultrastructural changes are identical to those observed in X-linked SA. However, some signs clearly indicate recessive inheritance: consanguineous marriages, severe disease in female patients, absence of severe disease in parents, microhematuria in the father. The disease, as a rule, progresses early to ESRD, hearing impairment is almost always encountered, and not always - damage to the organ of vision.

Among heterozygotes, constant or intermittent microhematuria is noted.

Autosomal dominant Alport syndrome

Autosomal dominant inheritance, characterized by transmission through the male line, is rare. The clinical phenotype is the same for men and women. The course is milder than the X-linked form, with late and variable progression to the development of ESRD and hearing loss. Heterozygous mutations in the COL4A3 or COL4A4 genes have been identified in some families.

Diagnosis and treatment of Alport syndrome. Diagnosis of SA and determination of the type of inheritance are important for therapeutic management, prognosis and medical genetic counseling of patients and their families. The issue is easily resolved if hematuria is combined with deafness or eye lesions and if the hereditary history is sufficiently informative to establish the type of inheritance. Each incidentally discovered hematuria requires examination of other family members. Early onset of hematuria and detection of sensorineural hearing loss, lenticonus, or maculopathy upon careful examination may provide guidance regarding AS, but the mode of inheritance remains uncertain. Identification of mutations in the COL4A5, COL4A3, or COL4A4 genes is critical for disease diagnosis, but molecular analysis is expensive and time-consuming due to the large size of the type IV collagen gene and the wide variety of mutations.

It is important to differentiate Alport syndrome early from thin basement membrane disease (TBMD). This is best done on the basis of family history: the presence in the family of adult men over 35 years of age with hematuria and preserved renal functions with a high probability allows us to settle on the diagnosis of BTBM.

In the absence of hearing loss, diagnosis is quite difficult: if you do a renal biopsy too early (before 6 years), you may not see the changes characteristic of Alport syndrome, which will develop later, and electron microscopy is not available everywhere. In this regard, the introduction of an immunohistochemical method for determining the expression of various type IV collagen chains in renal tissue or skin is promising.

Sporadic hematuria with proteinuria, detected in the absence of extrarenal manifestations, is the reason for a renal biopsy to exclude other hematuric glomerulopathies (IgA nephropathy, etc.). Progression to end-stage renal disease is inevitable in X-linked AS in men and in all patients with autosomal recessive AS. To date, there is no specific treatment. The main treatment is blockade of the renin-angiotensin system to reduce and possibly slow progression. Kidney transplantation leads to satisfactory results, however, about 2.5% of all patients with AS develop anti-GBM due to formation of the donor's “other” GBM, which leads to graft rejection.