Fanconi syndrome( full name - de Toni-Debreu-Fanconi) is a congenital pathology that manifests itself in severe dysfunction of the proximal renal tubules, namely, secondary absorption( absorption into the blood) of substances filtered by the kidneys, which leads to glucosuria( increased sugar inurine), phosphaturia( impaired metabolism of phosphorus and calcium), aminoaciduria( increased excretion of amino acids in the urine) and a decrease in the concentration of hydrocarbonates that regulate the acidity of the blood.
De-Tony-Debreu-Fanconi Syndrome
Fanconi Syndrome is a very rare disease, mainly found in children, and according to medical statistics, its frequency corresponds to 1 sick infant per 350,000 newborns of both sexes.
In adults, it is extremely rare to develop against the background of acquired pathologies. Pathology code according to ICD-10: E72.O.
Causes of
The nature and causes of the genetic defect of Fanconi syndrome have not been adequately studied today.
It is suggested that at the heart of the pathology lie either the defects of the transport proteins of the renal tubules or a gene mutation that distorts the function of enzymes regulating the reverse absorption of glucose, amino acids and phosphorus.
There are data on studies of point defects in mitochondria, which lead to improper functioning of the renal tubules.
The disease is also associated with intolerance to fructose, chronic poisoning with toxins( heavy metals, ifosfamide, aminoglycosides), vitamin D deficiency, amyloidosis, insufficiency of a number of cellular enzymes( pyruvate carboxylase, phosphoenolpyruvate carboxylase and others), tyrosinemia, metachromatic leukodystrophy, galactosemia, cystinosis, glycogenoses.
According to other experts, Fanconi syndrome can be an isolated pathology - namely - one of the most severe forms of rachitis-like pathologies that are hereditary.
Studies confirm that in the Fanconi syndrome, cellular energy metabolism involving ATP( adenosine triphosphate) and intercellular transport in the tubules of the main element of the kidney nephron is disrupted.
Since in medicine they have not yet come to an unambiguous conclusion about the causes of Fakoni's syndrome, this condition is also denoted by other terms: "glucophosphamide diabetes", "idiopathic renal Fanconi syndrome", "D-resistant rickets", "kidney nanism with D-resistant rickets"," Hereditary Fanconi syndrome. "
Forms and pathogenesis of
There are two types of Fanconi syndrome:
- is hereditary( congenital, idiopathic), which refers to the primary form;
- acquired, which is considered as a secondary form of the disease.
The hereditary( genetic) kind of specialists is associated with the defect of the X chromosome, which is inherited by the dominant and recessive type, so the genetic prognosis of its manifestation in the future offspring is not an easy task. If the pathology refers to the congenital( primary form) type, it is detected in the child in the breast period up to a year. Therefore, the primary form is called "infant".
The degree of gene mutation causes the degree of severity of the syndrome itself. So, the hereditary full Fanconi syndrome reveals itself in the presence of 3 basic biochemical defects, which include glucosuria, aminoaciduria, phosphaturia, incomplete - with two of them.
Usually genetically determined pathology is accompanied by other congenital ailments: cystinosis, Wilson syndromes, Denta, Lowe, fructose intolerance, tyrosinemia( inability of the body to efficiently cleave amino acid tyrosine), galactoseemia( sugar-glucose conversion dysfunction), excessive glycogen storage.
Acquired syndrome( secondary), unlike congenital, is not accompanied, but is a consequence of already existing pathologies:
- type I tyrosinemia;
- cystinosis( impaired metabolism of the amino acid cystine followed by kidney damage);
- fructose intolerance;
- Wilson-Konovalov's disease;
- galactosemia;
- glycogenosis( abnormal accumulation of glycogen in tissues and organs) type XI;
- hereditary renal pathology;
- amyloidosis( a violation of protein metabolism leading to sclerosis, atrophy, organ dysfunction);
- tubulointerstitial nephropathies( nephritis with tissue damage, renal tubules);
- hyperparathyroidism( endocrine disease, in which the normal content of calcium and phosphorus in the blood is disturbed);
- malignant formations: myeloma, ovarian, lung, pancreatic, lung, lung disease, lymphogranulomatosis;
- deep burns.
In addition, the syndrome can provoke such conditions:
- organ transplantation with low tissue compatibility;
- deficiency of vitamin D;
- poisoning with uranium, bismuth, mercury, lead, cadmium;
- contact with toluene, maleic acid, lysol;
- use of nephrotoxic pharmacological agents such as: Gentamicin, platinum drugs, tetracycline-based overdue medications, didanosine, cidofovir, anticancer chemotherapy drugs - Ifosfamide, Streptozocin.
Symptoms and signs
In hereditary( congenital) form
Primary symptoms are manifested in the first months of life, rarely - after a year and a half.
First of all, the following conditions are noted in a newborn child:
- frequent urination( polyuria);
- increased thirst( polydipsia);
- prolonged constipation;
- frequent attacks of causeless vomiting;
- asthenia( general fatigue), muscle weakness;
- unexplained "temperature jumps" up to 37.5 - 38 C;
- bloated tummy.
As a rule, during the period when the onset of vomiting and temperature rise of the baby are shown to the pediatrician. An experienced specialist should determine that the combination of disturbing parents of signs is not related to ARI, ARVI or enterovirus infection.
After mild and rather vague symptoms in the following year - one and a half clearly recorded symptoms typical of Fanconi syndrome:
- Early Nanism( short stature), caused by the constant elimination of the most important amino acids, glucose, calcium, phosphates from the body. The first six months of normal growth and weight are replaced by a deficit of body weight( up to 30%) and growth( from 2 to 21%).
- Rickets caused by massive excretion of calcium and phosphates become noticeable after 10 to 12 months of life, and has features characteristic of the Fanconi syndrome: the baby's head is usually slightly deformed, but the large bones of the legs and arms show significant curvatures - deformities in the varus type,the baby is bent "wheel", or valgus( in the form of the letter "X").Twist and bones of the chest, spine.
- Delay in mental and physical development.
- Uncommunicability, fearfulness, lack of consistency.
- Polydipsia and polyuria can progress and regress without passing definitively.
- Moderate muscular hypotension, expressed in slowness, difficulty in movement, leading to the fact that children 5-6 years old are unable to walk.
- Pain in bones, moderate intensity, interfering with the child's walking. Stronger at the level of the legs, pelvis and spine. Gait, if a child walks, becomes a "duck", unsure.
- High probability of fractured tubular bones due to a deficiency of minerals in bone tissue.
- Osteomalacia or softening of bones due to destruction of bone tissue as a result of lack of calcium and phosphorus salts.
- Reduced immune defense against infections, which is manifested in frequent viral diseases, otitis, pneumonia.
- Paralyzes caused by lack of potassium.
- Ophthalmic pathologies, such as: retinitis pigmentosa, congenital cataract.
- Development of pathologies of the nervous system, ENT( ear, nose, pharynx, larynx) and gastrointestinal organs, cardiovascular system, anatomical abnormalities of the urinary system due to massive metabolic disorders.
- In isolated cases, endocrine disorders of
In the course of progression of tubular disorders( disruption of transport of organic substances, minerals, electrolytes) to 10-12 years in children, the probability of developing chronic renal failure is increased, which threatens his life.
In adult patients with secondary
development If the acquired Fanconi syndrome develops in adults with other diseases or pathological conditions, its manifestations are often combined with manifestations of a provocative disease.
Nevertheless, the following basic signs are revealed:
- Increased urine volume per day( up to 2 liters and more) and acute thirst, also characteristic of patients of early childhood.
- General and muscle weakness, bone pain.
- High probability of persistent increase in blood pressure( hypertension) on the background of renal dysfunction.
- Osteomalacia( destruction of bones).
- Acidosis( increased blood acidity) due to delayed oxidation products in the body, leading to hypokalemia( potassium deficiency).
- Nephrocalcinosis is a high deposition of calcium salts in the kidneys with fever, chills, nausea, severe pains in the abdomen, groin, ovaries characteristic for this condition.
- Hypokalemia( low potassium intake), causing severe heart complications, including life-threatening arrhythmias.
- Fast( if untreated) formation of chronic kidney deficiency
In women
The most unfavorable variant of the Fanconi syndrome is realized in its development in women in the postmenopausal period. At this time, against the background of a decrease in the production of hormones, there is a natural decrease in bone density( osteopenia).
When this condition is combined with increased bone fragility due to a lack of minerals, there is a high probability of severe compression fractures of the vertebrae, cervical neck and subsequent disability.
Diagnosis
In order to correct or refute the diagnosis, with the help of renategography, bone examination and in-depth biochemical studies of blood and urine are performed.
Laboratory
Detected changes in urine and blood biochemistry:
| Characteristics of | Indicators of |
|---|---|
| low calcium and phosphorus content of | of less than 2.1 mmol / L and 0.9 mmol / L, respectively |
| acidosis( acidification of blood) | BE = 10 -12 mg / dL |
| Glucosuria( increase in sugar in the urine) | 2-3% and above |
| hyperaminoiduria( urinary excretion of important amino acids alanine, arginine, glycine, prolate) | up to 2 - 2.5 g / day |
| excretion of calcium in the urine | 1,5 - 3,5 mmol / day |
| increase in pH( acidity) of urine due to an anomalyvery high loss of bicarbonates | to 6.0 |
| increase in the relative density of urine | 1,025 - 1,035 |
The examination also reveals:
- increased alkaline phosphatase activity;
- excessive excretion of sodium, potassium salts from the body;
- proteinuria( appearance of protein in the urine) in the presence of light chains of immunoglobulins, lysozyme, low-molecular proteins, beta 2-microglobulins;
- increase in the clearance( rate of filtration) of uric acid with its reduced serum content
- a decrease in the activity of energy-exchange enzymes: succinate dehydrogenase, a-glycerophosphate dehydrogenase, glutamate dehydrogenase;
- increase in blood levels of lactic and pyruvic acid.
Instrumental
Diagnosis of Fanconi syndrome requires mandatory use of bone radiography to detect deformity of the skeleton, extremities, detection of signs of osteomalacia, osteoporosis, and in children - additionally - bone growth retardation in comparison with the norm according to the calendar age.
The following abnormalities in bone tissue are observed:
- is coarse-grained, cellular structure with lacunae, poor mineralization, abnormal growths in the form of "thorns" in the femoral and tibia;
- signs of epiphysiolysis( partial or complete arrest of bone growth in length in the unripe skeleton, resulting in asymmetry of the limbs);
- fractures of tubular bones( at a late stage) against the backdrop of osteoporosis, the extent of which is determined by X-ray densitometry;
- accumulation of radioisotope in areas of intense bone growth.
In the kidney:
In the electronic study of a biopsy of the kidney tissue( biopsy), a characteristic change in the shape of the tubules in the form of a "swan neck", thinning, atrophy( decrease in volume) of epithelial tissue in the presence of an increased amount of mitochondria in it, fibrosis( abnormal proliferation) of connective tissue.
Necessary research:
What organs are examined
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