Wilson-Konovalov's disease

Description:

Wilson-Konovalov's disease (hepatolenticular degeneration)  - a rare hereditary disease which cornerstone disturbance of metabolism of copper and its accumulation in a liver and other internals is. The disease proceeds with preferential damage of a liver and TsNS, involvement in pathological process of an organ of sight and kidneys.

Symptoms of the Disease of Wilson-Konovalov:

Allocate three stages of a disease:

    * I - latent with nonspecific morphological changes of a liver or small - or srednekapelny fatty dystrophy;
    * II - HAG;
    * III - a cirrhotic stage.

Perhaps long subclinical current at which find in punctates of a liver necroses of single hepatocytes, fatty infiltration, periportal fibrosis.

At patients with clinically latent current the diagnosis is made at identification of characteristic changes of indicators of metabolism of copper:

  1.snizheniya plasma ceruloplasmin level (< 0,2 г/л),
  2.chasto in a combination to decrease in concentration of free copper of blood (norm of 13,4-24,4 µmol/l) owing to decrease in fraction of the copper connected with ceruloplasmin and increase (> 100 mkg/days) copper excretion with urine.

Patognomonichno existence of a corneal ring about 2 mm wide of Kayser-Fleischer owing to accumulation of the knutra pigment containing copper, grayish-brown with a greenish shade, from a limb on a back surface of a cornea. It best of all comes to light by means of a slit lamp.

At most of patients define a hepatomegalia and more than at 50% - a splenomegaly. 5% of patients are younger than 35 years with picture HAG of not clear etiology have Wilson-Konovalov's disease. Therefore at all young sick HAG definition of indicators of exchange of copper is reasonable. Hepatitis can proceed with astenisation, jaundice, an abdominal pain and the dispepsichesky phenomena, a hyper aminotransferasemia, a hypoalbuminemia and a moderate hypergammaglobulinemia. Often observe lengthening of a prothrombin time, hemorrhagic diathesis, hemolysis. The bone and joint syndrome with osteoporosis or osteomalacy, defeat of knee joints and a backbone is possible. Damage of kidneys is shown by peripheral hypostases, a microhematuria, insignificant proteinuria, increase in concentration of urea and creatinine of blood. Disturbance of a reabsorption at the level of proximal tubules and in this regard a hyper aminoaciduria, a hypercalcuria, a hyperphosphaturia, increase of excretion with urine of uric acid and sodium is often observed. Defeat of distal tubules with development of renal canalicular acidosis is possible. Patients at whom Wilson-Konovalov's disease debuted the picture of an acute hepatitis or a fulminantny liver failure with the phenomena of hemolysis which developed after a grippopodobny episode or the period of dispepsichesky disturbances are described. Also acute renal failure caused by massive hemolysis can be initial display of a disease.

The final stage of a disease of Wilson-Konovalov - a stage of the created cirrhosis, is more often makronodulyarny, with accumulation of copper in periportal spaces and along fibrous sept. Cirrhosis often is followed by a hypersplenism with thrombocytopenia and a hemorrhagic syndrome.

Early neurologic displays of a disease at adults - a tremor and the dysarthtia reminding a scanning speech, involuntary sharp turns of the head and a look in the same party, lacks of coordination of movements, esobenno noticeable when walking, a dysphagy, dystonia.

Etiologies of Wilson-Konovalov:

The disease has a hereditary etiology. It meets frequency of 1:200000, is transferred by fathers carriers of the corresponding gene autosomalno-retsessivno. Heterozygotes due to illness of Wilson make about 1% of clinically healthy faces. They are carriers of a pathological allele and can find anomalies of metabolism of copper. At recessive inheritance 25% of sons of parents carriers of a defective gene get sick, and 50% become healthy carriers. Symptoms of a disease are found in most of patients aged from 5 up to 30 years.

Treatment of the Disease of Wilson-Konovalov:

Treatment of a disease of Wilson is directed to removal of excess of copper from an organism for the prevention of its toxic influence.

At treatment of a disease of Wilson the diet No. 5 rich with protein, with restriction of the products containing copper is applied: mutton, chicken meat, duck's flesh, sausage, fish, Crustacea, champignons, garden cress, sorrel, leek, garden radish, bean nuts, prunes, chestnuts, chocolate, cocoa, honey, pepper, etc. The drugs connecting and bringing copper out of an organism are used.

At treatment of a disease of Wilson the BALL — the British anti-lewisite (2,3-dimerkap-topropanol) is applied, 2 times a day within 10 — 20 days, a break between courses of 20 days are entered intramusculary on 1,25 — 2,5 mg/kg. Other technique of use: introduction of 200 — 300 mg 2 times a day within several months before obtaining effect. Use of drug is limited because of morbidity of injections and emergence of symptoms of intoxication at prolonged treatment.

At treatment of a disease of Wilson Unithiolum (5% solution), on 5 — 10 ml daily or every other day, on a course 25 — 30 intramuscular injections is applied. Repeated courses in 2 — 3 months.

In treatment of a disease of Wilson in addition to a diet with an exception of cupriferous products use medkhelatiruyushchy drugs (D-Penicillaminum). However they are contraindicated at a cirrhosis stage. Instead of it zinc drugs are appointed.

D-Penicillaminum gained the greatest distribution at treatment of a disease of Wilson. The doses recommended by various authors at treatment of a disease of Wilson make from 0,3 — 1,3 to 3 — 4 g/days. An optimum dose of drug 0,9 — 1,2 g/days. Treatment is carried out for life. In some cases at treatment of a disease of Wilson quite bystry smoothing of neurologic symptomatology under the influence of treatment is noted. At treatment by D-Penicillaminum hematologic, renal and skin complications are possible. A malignant agranulocytosis, passing trombo-and a leukopenia are most often observed in the first 6 weeks of treatment of a disease of Wilson, and check analyses of blood at first do 2 times a week, and then once a month. The nephrotic syndrome is observed usually during the period of 2 months at use of glucocorticoids. Skin complications at treatment of a disease of Wilson — a local or generalized erythema, urtikarny rashes, hemorrhagic skin extravasates, a xeroderma of the person; at very prolonged use of drug sometimes there are deep extremity ulcers, is more often on shins. The termination of reception of D-Penicillaminum leads to disappearance of skin complications. From other complications at treatment of a disease of Wilson the dispepsichesky phenomena, decrease or loss of taste are possible. As a contraindication to treatment as D-Penicillaminum of a disease of Wilson serve the leukopenia, thrombocytopenia, and also a prekoma and a coma.

In treatment of hepatocerebral dystrophy widely apply B1 and B6 vitamins as at this disease excess amounts of copper block their activity. The drugs improving exchange of hepatocytes are shown.

Transplantation of a liver is shown only in exceptional cases — seldom only method which can save life to the patient.