Neurological manifestations of fanconi disease in children. Fanconi syndrome: signs and treatment. Treatment with medication

From the book Ancestral Syndrome: Transgenerational Connections, Family Secrets, Anniversary Syndrome, Trauma Transfer, and the Practical Use of the Genosociogram / Per. I.K. Masalkov - Moscow: Publishing house of the Institute of Psychotherapy: 2001 To the therapists of the Philadelphia school, which contributed

DEJA VU SYNDROME DEJA VU SYNDROME From stability - to disintegration or to development? Mikhail Delyagin 09/05/2012

It should be differentiated from the real syndrome in hypervitaminosis D, in which, as a result of enzymatic deficiency of the tubular apparatus of the kidneys, severe metabolic disorders develop in the child's body. V. V. Shitskova et al. (1971) on the basis of their own observations give the following differential diagnostic table of these diseases (Table 7) with some of our additions.

Fanconi syndrome- amine diabetes. Disorder of cystine metabolism, accompanied by glycosuria, aminoacidouria, phosphaturia, increased excretion alanine, loss of alkalis. It is caused by a hereditary defect in the renal tubules, which makes it impossible to reabsorb glucose, amino acids and phosphatone. The exchange of cystine is upset, which is deposited in the form of crystals in the reticuloendothelial system, cornea, renal tubules and other tissues. This leads over time to progressive insufficiency. various functions renal tubules.

It is necessary to distinguish Fanconi's syndrome from cystinuria, in which cystine is not deposited in the tissues. With the syndrome functional ability glomerular apparatus remains normal. The serum calcium concentration is normal, the level of inorganic phosphorus drops sharply. On the radiograph, osteomalacia and diffuse depletion of the bones with alkali are noted.

Fanconi syndrome (or de Toni-Debre-Fanconi) is a kidney disease characterized by protein and ion reabsorption during primary urine concentration and associated metabolic and permanence disorders. internal environment. Defects in the renal tubules lead to the fact that glucose, phosphates, amino acids and bicarbonates are excreted from the body.

Epidemiology and causes

Fanconi syndrome occurs in all parts of the world, and the frequency of its occurrence is one in 350,000 births. This is quite common, if we take into account the planetary scale.

This disease can be either congenital or acquired as a result of the progression of other diseases. Scientists have not yet fully determined what kind of genetic defect causes the appearance of such biochemical shifts. There is a theory that due to damage to the proteins that make up the membranes of the renal tubules, their permeability is impaired. Another hypothesis states that the mutation affects the enzymes that reabsorb glucose and micronutrients.

Allocate full and incomplete syndrome Fanconi. If all three biochemical components are damaged, then they speak of a complete syndrome, if only two of the three, then this is an incomplete, or partial, syndrome.

Risk factors

Fanconi syndrome is rarely seen on its own. Most often, it is associated with diseases such as cystinosis, galactosemia, systemic or congenital glycogenosis, tyrosinemia and other accumulation pathologies. In addition, poisoning with phosphates, aminoglycosides, large doses tetracyclines and heavy metals.

Amyloidosis, vitamin deficiency can also be harbingers of the syndrome. And some authors are inclined to think that the disease can be attributed to a severe degree of rickets-like pathologies.

Pathogenesis

Fanconi syndrome, or glucoaminophosphate diabetes, which is more common in domestic authors, develops due to a violation of the transport of substances through the membranes of the renal tubules. The cause of this condition has not yet been fully elucidated by pathophysiologists, but its consequences are well known.

Secondary changes in the body, resembling rickets, are the result of prolonged acidosis and a decrease in the level of phosphorus in the blood, as well as a decrease in the amount of ATP (adenosine triphosphate).

There are congenital and acquired Fanconi syndrome. The first, as a rule, is combined with fermentopathy, fructose intolerance, pathological accumulation of glycogen. Acquired syndrome is the result of taking toxic drugs, such as chemotherapy, cytostatics, or antiretroviral drugs. In addition, this symptom complex may appear after a kidney transplant, with amyloidosis and multiple myeloma.

Fanconi syndrome in adults

As a rule, primary or congenital, it is detected in childhood. In adults, Fanconi syndrome appears as a secondary disease after serious poisoning, difficult to tolerate treatment. It can also be a complication of systemic diseases.

With Fanconi's syndrome, glucose, phosphorus, proteins and other necessary substances are excreted in the urine of a patient. In this case, the amount of fluid lost is greater than normal, the density of urine decreases. Patients complain of weakness and pain in muscles and bones, lethargy, drowsiness.

Most often, secondary Fanconi syndrome affects women after fifty-five years. Against the background of an already reduced level of calcium, there is a loss of phosphorus and other trace elements. This provokes the development of osteoporosis and, as a result, compression fractures of the vertebrae, complex fractures of tubular bones. Ultimately, the patient may remain disabled.

Symptoms in children

Most often and clearly you can see the Fanconi syndrome in children. Symptoms appear already in the first year of life and at first they are similar to those in adults:

• polyuria (increased amount of urine);
• polydipsia (the baby drinks a lot of liquid);
• subfebrile temperature, vomiting and constipation.

Due to the constant loss of vitamins, trace elements and sugars, the child begins to lag behind in mental and physical development from their peers. The doctor can observe the curvature of the bones of the legs, a decrease in muscle tone, followed by their atrophy, to the point that five-year-old children cannot walk on their own. The disease progresses with age and puberty the child develops chronic renal failure.

Sometimes there are also manifestations of the disease from other systems, for example, damage to the eyes, central nervous system, heart and blood vessels. May be combined congenital anomalies genitourinary system, ENT organs and gastrointestinal tract.

Classification

Clinically, primary and secondary Fanconi syndrome are distinguished, respectively, there are their types and subspecies.

Idiopathic syndrome is divided into:

• hereditary;
• sporadic (spontaneous mutation in healthy parents);
• Dent's syndrome.

The classification of secondary Fanconi syndrome is associated with a group of primary pathology.

Metabolic disorders:

• cystinosis;
• tyrosinemia, glycogenosis, galactosemia;
• fructose intolerance.

Acquired pathologies of the kidneys:

• paraproteinemia;
• tubulointerstitial nephritis;
• neurotic syndrome;
• kidney damage after transplantation;
• paraneoplastic syndrome.

Also, the syndrome is observed with intoxication with heavy metals, poisoning with organic poisons, antibiotics, toxic drugs, burns of the third or fourth degree.

As can be seen from the above classification, the loss of essential trace elements and proteins in the urine is rarely independent disease, as a rule, this is a complication of other pathologies.

Diagnostics

Symptoms of de Toni-Debre-Fanconi in children and adults are the reason for further diagnostic search. IN biochemical analysis blood doctor can detect a decrease in calcium, phosphorus, sodium and other trace elements against the background of an increase in the level of alkaline phosphatase (alkaline phosphatase). Since bicarbonates are lost in the urine, oxidation of the internal environment is observed. In the general analysis of urine, the presence of glucose, phosphorus, proteins and amino acids is noted. Urine has low density, it is a lot.

From instrumental methods X-ray examination of the bones is mandatory for diagnosing osteoporosis and pathological deformities, as well as examinations of foci of ossification, in order to see the lag of bone age from the passport one.

In addition, in some patients, it is recommended to use a radioisotope study or bone tissue scintigraphy. Areas of active bone growth will appear darker on the screen. This will allow the doctor to determine the severity of the disease.

To determine the degree of damage to the tissues of the kidneys, they are biopsied. It reveals characteristic shape tubules of the kidneys in the form of a swan neck, atrophy of the tubular epithelium, the presence of areas of tissue fibrosis.

Treatment

How should a doctor act after a diagnosis of Fanconi syndrome? Treatment of children begins the sooner the better. It is aimed at correcting electrolyte imbalance, replenishing the amount of proteins and buffer bases. Patients are recommended plentiful drink, special diet With high content micronutrients, limiting salt, and introducing alkalizing foods such as milk and fruit juices into the diet. In addition, children are advised to eat more dried fruits.

With secondary Fanconi syndrome, the symptoms are leveled after the treatment of the underlying disease. Sometimes, with severe bone deformities, consultation with trauma surgeons or orthopedists may be required. But this is only possible if there is a remission with the disappearance of all symptoms for more than a year and a half.

Prevention and prognosis

For the prevention of primary disease before pregnancy couples with a compromised family history should undergo medical genetic counseling. The probability of the appearance of a sick child in the family with a tendency to this pathology is 25 percent.

Syndrome de Tony-Debre-Fanconi in children and adults ends disappointingly. occur in the renal parenchyma irreversible changes which lead to the development of chronic renal failure and the need for dialysis.

Fanconi syndrome in Basenji: signs

Unfortunately, the syndrome occurs not only in humans. Fanconi syndrome can also manifest itself in certain breeds of dogs. Because the withdrawal purebred dogs associated with the accumulation genetic mutations, they have various hereditary diseases. One of them may be Fanconi syndrome. In this case, the animal progressively loses weight, muscle atrophy is observed. Due to pain in the bones, the dog becomes lethargic, weak, stops running and playing, tries to step on its paws less due to pain in the bones. Another symptom is excessive thirst and frequent urination.

Fanconi syndrome (glucose-phosphate-amine diabetes, de Toni-Debre-Fanconi disease, primary isolated syndrome Fanconi) - genetic disease, which developed as a result of an autosomal recessive mutation, characterized by impaired reabsorption of water and bioactive substances from primary urine (tubular reabsorption), due to damage to the renal tubules. Refers to a rickets-like group of diseases in which systemic metabolic changes occur.

Causes

Pathological changes represent one of the forms of hyperparathyroidism - an endocrine disorder that develops with excessive production of parathyroid hormone (produced parathyroid glands) as a result of hyperplasia of the glands or malignant lesions.

Inheritance options for de Toni-Debre-Fanconi syndrome:

1. Autosomal dominant - the defective gene is inherited from one of the parents (family form).
2. Autosomal recessive - the defective gene is present in both parents. In the case of the syndrome, we are talking about a local form of autosomal recessive inheritance (chromosome 15q15.3.)

Fanconi syndrome in children can be a component of other genetic diseases:

1. Cystinosis is an excessive accumulation of cystine (an amino acid) in the cytoplasm (internal liquid cell environment) of a cell.
2. - a violation of the conversion of galactose (monosaccharide) into glucose, due to a mutation of the gene responsible for the production of galactose-1-phosphate uridyltransferase (enzyme).
3. Type I tyrosinemia is a deficiency of fumarylacetoacetate hydrolase, resulting in impaired tyrosine metabolism.
4. - severe hepatocerebral dystrophy due to impaired copper metabolism.
5. fructose - loss of the enzyme as a result of malabsorption of fructose, its intolerance, due to a deficiency of the fructose transporter protein.

It has been established that the pathology is based on combined tubulopathy - a group of diseases in which the transport of biologically active substances in the tubular system is impaired. The main link in the mechanism of development of Fanconi syndrome is a defect in mitochondria (energy depot of the cell) in the tricarboxylic acid cycle (Krebs cycle), which is a key stage in cell respiration.

The stages of the disease development mechanism, where each subsequent stage will be a consequence of the previous one, can be represented as follows:

1. Mitochondrial defect, enzymatic tubulopathy.
2. Violation of the reabsorption of amino acids and enzymes in the tubules of the kidneys.
3. Accumulation of acids ().
4. Bone resorption (destruction).
5. Violation of the reverse absorption of calcium and potassium in the tubules.

Cells lose their energy supply, resulting in severe metabolic disorders. Risk factors include:

• heavy metal poisoning;
• toxic infections;
• taking expired tetracycline antibiotics;
• vitamin D deficiency;
• (violation of protein metabolism).

Classification

There are primary (idiopathic) and secondary forms of Fanconi's disease. The primary form develops as a result of the inheritance of a defective gene. The secondary form occurs with other congenital, genetically determined diseases.

The secondary syndrome can occur against the background of acquired pathologies:

• paraproteinemia - the presence of abnormal protein bodies in the blood;
• - severe disorders that develop with damage to the glomeruli of the kidneys;
• tubulointerstitial - a group of kidney diseases characterized by a primary lesion of the tubules;
• malignant neoplasm(paraneoplastic syndrome);
• in case of poisoning;
• severe burns.

Symptoms

Fanconi syndrome, the symptoms of which appear in children by the second year of life, has two development options, depending on clinical and laboratory parameters:

1. The first option is typical severe course, a pronounced lag in physical development, fractures and bone deformities as a result of hypocalcemia, malabsorption in the intestine.
2. The second option is a relatively mild course, moderate signs of a delay in physical development, bone deformities during normal level calcium, absorption of calcium in the intestine is within the normal range.

The first symptoms of the disease in children under two years of age:

• a sharp decrease in appetite;
• deficiency of body weight;
• lethargy;
• (indigestion caused by protein-energy deficiency);
• thirst;
• low blood pressure;
• (a large number of urine);
• subfebrile temperature;
• vomit.

These children are unable to walk by the age of five.

At the height of the disease by the age of five or six, the first sign will be (bone softening), bone deformities, paralysis associated with a lack of calcium.

After the appearance of the first signs, there is a lag in mental and physical development. Generalized (spread throughout the body) decalcification is manifested by deformities lower extremities (hallux valgus- inward curvature, varus - outward curvature), loss of muscle tone, curvature chest, bones of the forearms and shoulders. The lack of phosphorus in children leads to the appearance.

With the progression of the syndrome in children, visual disturbances, diseases of the nervous system, urinary and digestive system, diseases of ENT organs. Rarely occur.

With Fanconi syndrome in adults, osteomalacia occurs due to a deficiency of minerals and trace elements. Patients complain of bone pain, muscle weakness, lethargy, possibly increased blood pressure, the development of renal failure in the absence of therapy.

In children early age even in the first weeks of life, signs of the Wissler-Fanconi syndrome may occur due to severe allergic reaction. Pathology is characterized by fever, erythematous rash, joint damage (usually hands).

Diagnostics

To detect Fanconi disease, laboratory and visual methods diagnostics. A biochemical blood test reveals a lack of calcium and phosphorus, beta-2-microglobulin (low molecular weight protein). In the urine, aminoaciduria (metabolic products of amino acids), renal (electrolyte disorders), glycosuria (sugar in urine), a large amount of phosphates, a deficiency of trace elements (sodium, calcium, potassium, phosphorus and others) are detected.

plays an important role in assessing renal function ultrasound examination and MRI.

X-ray examination of bones allows you to study the bone structure, detect structural disorders, the degree of osteoporosis, deformity, and assess the age lag in the development of bone tissue. With Fanconi's disease, radiography reveals:

• coarse fibrous bone structure;
• - destruction of the epiphyseal (cartilaginous) growth plate;
• cellular structure and spur-like growths in the tibia;
• and fractures - in the later stages.

In a positron emission study (PET), the accumulation of a radioisotope substance in the growth zones of the patient's bones is detected.

In the biopsy material, a violation of the structure of the bone, lacunae (pathological depressions), poor mineralization are found.

In glucose-phosphate-amine diabetes, differential diagnosis with the following pathologies:

• cystinosis;
• glycogenosis;
• different syndromes (Low, nephrotic);
• multiple myeloma (malignant blood disease);
• fructose intolerance due to a genetic factor, other hereditary diseases;
• conditions arising from kidney transplantation.

Treatment

Fanconi syndrome is treated by a hematologist and geneticist. With abnormalities in the structure of the renal structures, severe proteinuria, consultation with a urologist and nephrologist is necessary, with endocrine disorders - an endocrinologist, with visual impairment - an ophthalmologist.

Therapy is aimed at:

• elimination of electrolyte disturbances, in particular tubular acidosis;
• correction of acid-base imbalance;
• elimination clinical manifestations(symptomatic therapy).

The course is prescribed potassium and calcium preparations, vitamin D with a gradual increase in dosage and a blood test in dynamics for the content of phosphorus and calcium. Plentiful drink and a diet are recommended. In nutrition, you should limit the consumption of salty foods and salt, introduce milk, dried apricots, prunes, fruit juices into the diet. With the normalization of blood counts, you can do massage, take coniferous baths.

Surgical intervention is indicated only for severe bone deformities. The operation is performed with a stable remission lasting from one and a half years, which is confirmed by diagnostic indicators and clinical manifestations.

Most severe complication glucose-phosphate-amine diabetes -. With a severe degree of the disease that threatens the patient's life, hemodialysis ("artificial kidney") is indicated.

For some types of kidney failure, hemodialysis is done temporarily until the kidney function improves or restores. In other cases, with irreversible processes in the kidneys, the procedure is carried out for life.

Dialysis consists in passing blood through a special system, where toxic substances are separated from the biofluid, which are removed using a dialysis solution. The body is freed from toxic decay products until the next accumulation.

Forecasts

The prognosis depends on the underlying disease, against which the syndrome developed. If the underlying disease is a neoplasm, if it is successfully removed, the prognosis may be relatively favorable.