Hepatolenticular degeneration( Wilson-Konovalov disease)
The disease is inherited by autosomal recessive type and is one of the most important causes of severe liver damage in childhood. The disease is usually of a family nature, therefore, a hereditary conditioned defect is expressed, which is expressed in a reduced formation in the liver of a transport protein that binds copper( ceruloplasmin) in the blood. The basis for the violation of excretion of copper at the molecular level has not been fully studied at the present time. In addition to ceruloplasmin, the liver and other organs contain metallothionein - a sulfur-containing protein that has an affinity for copper. It can play a role in intracellular transport of copper, its accumulation and utilization. The levels of ceruloplasmin, metallothionein and copper are stabilized by the age of two.
Phenotypic signs of Wilson-Konovalov's disease begin to appear at the age of 4 years, when the systems responsible for maintaining a constant level of copper and its excretion with bile are already being formed and ripening. Along with this hypothesis, there are others explaining the violation of the excretion of copper from the anomaly of metallothionein, as well as the defect of the regulator gene, as a result of which the fetal( same as in the fetal) metabolism of copper remains.
The classical form of Wilson-Konovalov's disease is represented by a triad of disorders: neurological disorders, Kaiser-Fleischer rings( green-brown color of the corneal limb) and cirrhosis of the liver( there is a primary accumulation of copper in the liver, brain, cornea, kidneys).
Usually, the first manifestation of the disease is dystonia, manifested by increased muscle tone, stiffness, speech disorders, changes in handwriting or difficulties in playing musical instruments.
With a different form of the disease( the Westfal-Strumpell variant), a large-scale tremor of wrists and shoulders predominates, convulsions, neuropsychiatric disorders with aggressive behavior are sometimes observed.
Dysfunctions of the liver at the age of 6-14 years occasionally take the form of fulminant hepatitis, but the most common is not so acute current that mimics chronic active hepatitis with weakness, fatigue, rapid exhaustion, jaundice, decreased appetite, increased liver and spleen and biochemical changesindicators of liver function. In persons with Wilson-Konovalov's disease( in older children with enlarged liver) all the characteristic manifestations of Fanconi syndrome appear, accompanied by an increase in the amount of glucose, uric acid, calcium and phosphorus in the urine. The disease is characterized by low concentrations of copper and ceruloplasmin in the blood serum, as well as a steady increase in the daily amount of copper withdrawn in the urine. Determination of the amount of copper in liver tissue obtained by biopsy finally confirms the diagnosis, but in heterozygous carriers of the mutant gene and patients with liver diseases, the concentration of copper can exceed the lower limit, adopted as a diagnostic criterion for Wilson-Konovalov's disease.
It should be noted that low concentrations of copper and ceruloplasmin in the blood are characteristic of all healthy newborns and some patients with eating disorders( including impaired intestinal absorption) and kidney disease. A liver biopsy is indicated to all patients who suspect Wilson-Konovalov's disease. Part of the material is used to quantify copper in the liver, and the other is subjected to histological examination. Changes in the liver are nonspecific, but in combination with clinical and laboratory data help to make the correct diagnosis.
Treatment. The disease is treated mainly with D-penicillamine, which forms a soluble complex with copper, easily excreted in the urine, it removes excess copper from the liver. The drug is taken in a daily dose of 1.5-2.0 g for a long time( even after the content of copper in the urine reaches a normal level).In most patients, the excretion of copper in the urine is normalized within 6-12 months, which is accompanied by an improvement in the functional state of the liver, the nervous system, and the disappearance of the Kaiser-Fleischner rings. Complications in the treatment of D-penicillamine can be a variety of diseases: leukopenia, fever, rash, lymphadenopathy, aplastic anemia, membranous glomerulonephritis, which usually develop very rarely and require the drug to be discontinued before they disappear;after which the drug is resumed. The introduction of corticosteroids helps prevent recurrences of complications. It requires additional administration of vitamins, in particular vitamin B6.
The prognosis of the disease is largely determined by the timeliness of the treatment, which in turn is characterized by the timing of the diagnosis, and also depends on the patient's individual sensitivity to the drug. Optimum results are achieved when patients begin to be treated in the asymptomatic period of the disease. Patients with acute hepatic insufficiency, severe lesion of the neuromuscular system, formed cirrhosis of the liver are usually extremely difficult to treat.
Among the metabolic disorders leading to the development of hepatic hepatosis, the deficiency of the inhibitor of the enzyme trypsin and other proteolytic enzymes is isolated. This substance( glycoprotein) is synthesized in the liver.
The main clinical manifestations of pathology in children under 3 months of age are cholestatic jaundice and liver enlargement( hepatomegaly).Along with a non-specific increase in serum levels of bilirubin, enzymes( transaminases and alkaline phosphatase), a decrease in the activity of the protein A1-inhibitor is observed to 10-20% of the norm. Other histological signs of the disease are quite variable and may include biliary hypoplasia, inflammation in the hepatic vein, etc.
In most children with a1-antitrypsin deficiency, cirrhosis develops, in adults, the risk of developing carcinoma of the liver increases significantly.
Treatment is reduced to hepatoprotective measures with periodic use of proteolysis inhibitors.