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This illness inherited on autosomal recessively type — one of the important reasons of a severe damage of a liver at children and young adults. The essence of pathological process consists that copper excretion with bile and therefore it collects in tissues of a liver, brain, kidneys and an iris of the eye of an eye is broken. — Konovalova it is necessary to think of Wilson's illness in each case of an illness of a liver at the child as its early recognition is important for the patient and his sibs.
Pathogeny. The molecular basis of disturbance of excretion of copper is unknown. Except ceruloplasmin, the liver and other bodies contain metallotionein — the sulfur-containing protein having affinity to copper. It can play a role in intracellular transport of copper, its accumulation and utilization, but its communication with the tseruloplazminovy mechanism of transport of copper is not clear. Normal the liver of a fruit and the newborn is rich metallotioneiny and copper while serum of children of chest age contains not enough ceruloplasmin. However at babies copper in extrahepatic fabrics does not accumulate and they have no symptoms of poisoning with this metal. Level of ceruloplasmin, a metallotionein and copper is stabilized to two-year age. Phenotypical symptoms of an illness of Wilson — Konovalova begin to be shown at the age of 4 flyings when the systems responsible for a homeostasis of copper and its excretion with bile have to ripen. Along with this hypothesis there are others which explain disturbance of excretion of honey with anomaly of a metallotionein, changes in lysosomes, and also defect of a regulator gene therefore the fetalis metabolism of copper remains.
Clinical manifestations. The classical form of an illness of Wilson — Konovalova is provided by a triad of disturbances: neurologic frustration, Kayser's rings — Fleischer and cirrhosis. However initial symptoms of an illness can be extremely variable as showed experience of inspection of 26 patients aged from 8 till 20 flyings. Normal level of aminotransferases is noted at 24% of patients, the normal content of ceruloplasmin — at 24%, Kayser's rings — Fleischer are not found in 24%, only in 50% of cases cirrhosis is revealed.
The most precursory symptoms of damage of a liver include (as their emergence) a hepatomegalia, a splenomegaly, jaundice and anorexia. Hypostases and ascites can suddenly develop, sometimes gastrointestinal bleeding becomes the first symptom of a disease. Cases when the illness debuted the hemolitic crises caused by toxic effect of copper on erythrocytes are known. In the beginning the clinical picture and morphological features can remind an acute viral hepatitis, the fulminant hepatitis created cirrhosis or, more often, chronic active hepatitis. At all uncured patients cirrhosis develops.
Neurologic signs can develop gradually or suddenly be shown. The intentsionny tremor, a dysarthtia and dystonia belong to frequent symptoms. Adjournment of copper in proximal tubules of kidneys leads to loss of glucose, amino acids, phosphates, uric acid and renal tubular acidosis.
Datas of laboratory. At most of patients deviations of hepatic functional trials, same as at chronic active hepatitis, the amount of copper and ceruloplasmin in serum is reduced are noted, and daily excretion of copper with urine is with firmness raised. The most reliable sign — the concentration of copper in liver tissue exceeding 400 mkg/g of dry matter. This indicator is much higher, than in the most started cases of chronic active hepatitis. The patient to whom the biopsy of a liver is contraindicated chreskozhno enter 64 SI; at the same time the characteristic distribution of isotope reflecting inability of ceruloplasmin to connect copper is noted and to send it to a blood channel.
Patomorfologiya. The biopsy of a liver is shown to all patients at whom Wilson's illness — Konovalova is supposed. The part of material is used for quantitative definition of copper, and another is subjected to histologic research. Changes in a liver are not specific, but in combination with clinical and datas of laboratory help to make the correct diagnosis.
In an initial stage of a disease observe fatty degeneration of kidneys, empty kernels ("glikogenovy" kernels) and acidophilic glybk (Mallori's little body), and in far come cases — extensive sites of cicatricial fabric and makronodulyarny cirrhosis.
Treatment. Excess of copper from a liver is deleted by means of D-Penicillaminum forming the soluble complex which is easily removed with urine with copper. Drug is accepted before food in daily: to a dose to 1,5 g; treatment is carried out constantly even after the content of copper in urine reaches normal level. At most of patients release of copper with urine is normalized within 6 — 12 months, it is accompanied by improvement of a condition of a liver and a nervous system, disappearance of rings of Kayser — Fleischer.
Side reactions on D-Penicillaminum at the persons having Wilson's illness — Konovalova, arise seldom. The most serious of them — aplastic anemia and a hymenoid glomerulonephritis, however are more often observed a leukopenia, fever, rash and a lymphadenopathy. Treatment of complications consists in drug withdrawal before their disappearance; then reappoint D-Penicillaminum in the increasing doses. Introduction of corticosteroids helps to prevent recurrence of complications. Treatment by D-Penicillaminum demands additional administration of vitamins, especially Bg vitamin. It is desirable to train school students in special classes, then their ability to write and study in general improve. It is possible to normalize gait and the movements sometimes with the help of psychotherapy.
Forecast. Uncured patients perish from neurologic, hepatic, renal or hematologic complications. The forecast at treatment by D-Penicillaminum depends on how treatment, and for individual reactivity is early begun. Optimum results are achieved when sibs of patients begin to treat during the asymptomatic period; in these cases it is possible to prevent emergence of symptoms. Patients with an acute liver failure or a severe defeat of the neuromuscular device usually refrakterna to treatment; at children with chronic active hepatitis the illness will badly respond to treatment and progresses in cirrhosis.