Hepatolenticular degeneration ( Wilson's disease )

August 12, 2017 17:51 | Genetic Diseases

The disease is inherited in an autosomal recessive manner and is one of the most important causes of severe liver disease in childhood.The disease usually runs in families, so assumed hereditary defect, manifested in reduced formation of a transport protein in the liver, blood copper binding (ceruloplasmin).The basis of violations of copper removal at the molecular level at the moment is not fully understood.Furthermore ceruloplasmin, liver and other organs contain metallothionein - sulfur-containing protein having affinity with copper.It may play a role in the intracellular transport of copper accumulation and its utilization.Levels of ceruloplasmin, metallothionein and copper stabilized to the age of two.

Phenotypic features Wilson's disease begin to be detected at the age of 4 years, when it forms a mature system and are responsible for maintaining a constant level of copper and its excretion in the bile.Along with this, there are other hypothesis to explain the violation excretion of copper metallot

hionein anomaly and control gene defect resulting in retained fetal (same as the fetus) copper metabolism.

classical form of Wilson's disease is represented by the triad disorders: neurological disorders, Kayser-Fleischer rings (green-brown color corneal limbus) and cirrhosis (occurs preferential accumulation of copper in the liver, brain, cornea, kidneys).

usually the first manifestation of the disease is a dystonia, which is manifested by increased muscle tone, stiffness, impaired speech, handwriting changes, or difficulty in playing musical instruments.

In another form of the disease (Westphal variant-Shtryumpellya) prevails krupnorazmashisty tremor wrists and shoulders, sometimes observed seizures, neuropsychiatric disorders with aggressive behavior.

impaired liver function in aged 6-14 years, sometimes take the form of fulminant hepatitis, but the most common are not so keen for that mimics chronic active hepatitis, with weakness, fatigue, rapid exhaustion, jaundice, loss of appetite, enlarged liver and spleen, and the changebiochemical parameters of liver function.In patients with Wilson's disease (in older children with an enlarged liver) there are all typical manifestations of Fanconi syndrome, accompanied by an increase in the amount of glucose, uric acid, calcium and phosphorus in the urine.Disease characterized by low concentrations of copper and serum ceruloplasmin and persistent increase in the daily amount of the urine derived copper.Determination of the amount of copper in the liver tissue obtained by biopsy confirms the diagnosis finally delivered earlier, but in heterozygous carriers of the mutant gene and patients with liver copper concentration can exceed the lower limit adopted as a diagnostic criterion for Wilson's disease.

It should be noted that low blood levels of copper and ceruloplasmin are common to all healthy newborns, and some patients with eating disorders (including disturbances of intestinal absorption), and kidney disease.Liver biopsy is indicated for all patients who have suspected Wilson's disease.Part of the material used for the quantitative determination of copper in the liver, and the other is subjected to histological examination.Changes in the liver are non-specific, but in conjunction with clinical and laboratory data to help make the correct diagnosis.

treatment. disease therapy is performed mainly by using D-penicillamine, which forms a soluble complex with the copper, the urine easily outputted, it removes excess copper from the liver.The drug is taken up in a daily dose of 1.5-2.0 g long (even after the copper content in the urine reaches the normal level).The majority of patients recovering copper in the urine normalized within 6-12 months, which is accompanied by the improvement of the functional state of the liver, the nervous system, the disappearance of rings Kaiser-Fleyshnera.

complications in the treatment of D-penicillamine can serve a variety of disorders: leukopenia, fever, rash, lymphadenopathy, aplastic anemia, membranous glomerulonephritis, which usually develop quite rare and require discontinuation of the drug prior to their disappearance;after which the drug is resumed.The introduction of corticosteroids help prevent recurrences of complications.It requires additional administration of vitamins, especially vitamin B6.

Prognosis timely treatment is determined to a greater extent, which in turn is characterized by the terms of diagnosis, but also depends on the individual patient's sensitivity to the drug.Optimal results are achieved when patients begin to heal in an asymptomatic period of the disease.Patients with acute liver failure, severe neuromuscular system, the generated cirrhosis usually amenable to treatment extremely difficult.

Among the disorders of metabolism, leading to the development of hepatic gepatoza, isolated deficiency of the enzyme trypsin inhibitor and other proteolytic enzymes.This substance (glycoprotein) is synthesized in the liver.

main clinical manifestations of disease in children under 3 months of age - cholestatic jaundice and liver enlargement (hepatomegaly).Along with the increase in the nonspecific serum bilirubin, enzymes (transaminases and alkaline phosphatase) marked decrease in activity of the protein-inhibitor a1 to 10-20% of normal.Other gistolicheskie symptoms are quite variable and may include underdevelopment (hypoplasia) of the bile duct, inflammation in the hepatic vein, and others.

Most children with failure a1-antitrypsin develop cirrhosis during adulthood in these patients significantly increases the risk of liver carcinoma.

Treatment is reduced to hepatoprotective activities with periodic use of proteolysis inhibitors.