Gepatoleptikulyarna a degeneration (gepatotserebralny dystrophy, or Wilson's illness — Konovalova) — the hereditary disease connected with disturbance of a metabolism of copper and which is shown damage of a liver and brain.
Etiology and pathogeny.
The disease is inherited on autosomal recessively type (both parents are almost healthy, but have in the genome on one mutant gene). The mutation in the gene located in the 13th chromosome leads to disturbance of synthesis of the liver enzyme which is carrying out copper excretion in bile and its connection with the carrier — ceruloplasmin. The copper collecting in an organism is laid in a liver, a brain, a cornea, kidneys. Neurologic symptoms are connected with toxic effect of copper on neurons basal gangliyev and a liver failure.
The beginning can be gradual or acute. At younger patients (till 20 flyings) the illness to a bowl begins with symptoms of damage of a liver, is more rare from an intravascular hemolysis and damage of kidneys (a nephrotic syndrome), a pancreas or heart. In the subsequent neurologic symptoms join. For lack of treatment the lethal outcome develops within several years. At the age of 20 — 40 the illness begins with neurologic or mental disorders more often: dysarthtias, a tremor, a chorea, dystonia, an ataxy, an akineziya, cognitive frustration (weakening of attention, memory, decrease in intelligence up to dementia) or emotional and personal disturbances (irascibility, impulsiveness, a maniacal state or, on the contrary, a depression and apathy) also proceeds more slowly. The tremor first can remind essential or parkinsonichesky, but becomes later more and more rough and quite often turns into a tremor of "fragile wings". In a clinical picture in one cases the akineziya and rigidity, in others — a tremor and an ataxy, in the third — hyperkinesias and changes of the personality prevail. At survey also increase and morbidity of a liver, symptoms of a liver failure are found.
Key diagnostic character of a gepatoleptikulyarny degeneration — an olive-brown corneal ring of Kayser — Fleischer, arising owing to copper adjournment. It comes to light at 95% of patients with neurologic manifestations and only at a third of patients with the isolated damage of a liver. Sometimes the ring can be seen with the naked eye, but more often it comes to light by means of a slit lamp. The diagnosis is confirmed also by decrease in content in ceruloplasmin blood, increase in excretion of copper with urine, decrease in the general content of copper in blood, increase in concentration in blood "free" (not connected with ceruloplasmin) to copper. In doubtful cases for confirmation of the diagnosis resort to a liver biopsy to reveal the increased content of copper.
Treatment is directed to removal of copper from cells and decrease in absorption of copper in intestines. Reduction of intracellular reserves of copper is provided by the drugs forming chelate connections with copper. Most often apply D-Penicillaminum (cuprenil) which patients are forced to accept during all life. At intolerance of Penicillaminum use also drugs of the zinc breaking absorption of copper in intestines. At the same time limit the use of the products rich with copper (mushrooms, a liver, chocolate, nuts, etc.). Against treatment only approximately full remission develops in 20% of cases, and most of patients has a considerable reduction of symptoms. But at small part of patients the disease progresses after an initiation of treatment. Usually deterioration is shown in the first 2 — 4 weeks, sometimes happens irreversible and, perhaps, is connected with release from a liver of a large amount of copper.