Etiology and Pathology:
• Wilson's disease is autosomal recessive and develops as a result of the ATP7B gene mutation on the 13th chromosome.
• Normally, dietary copper is absorbed from the gastrointestinal tract and enters the liver.
It is stored in the liver and given to the blood by binding to ceruloplasmin. Excess copper is removed from hepatocytes by secreting it into the bile.
• In Wilson's disease, the excretion of copper into the bile ducts and its binding to the blood by binding to ceruloplasmin are decreased. As a result, copper accumulates in the liver.
• Copper that rises above a certain concentration in the liver is released into the blood via exocytosis.
Copper circulating in the blood causes damage by accumulating mainly in the basal ganglia in the brain, eyes, kidneys and skeletal system.
• Since copper may not be found in the regenerative nodule, failure to show copper in the biopsy of a cirrhotic patient does not exclude the diagnosis of Wilson's disease.
Clinic:
• Symptoms usually begin between the ages of 5-30, and signs of liver involvement can be detected in childhood and early adolescence.
• In late adolescence, basal ganglia involvement and dementia develop.
• The findings of the disease can be examined in two groups as hepatic and extrahepatic.
Hepatic findings:
It can cause recurrent acute hepatitis attacks, fatty liver, acute hepatic failure, chronic hepatitis, cirrhosis and hepatocellular cancer (low risk of HCC).
Extrahepatic findings
They usually occur after liver damage has developed.
Neurological disease: The clinical picture is dominated by tremor, incoordination, choreoathetosis, dystonia, parkinsonism, dementia, dysarthria and dysphagia, which are signs of extrapyramidal involvement.
Psychological disorders: There may be behavioral disorders, depression, hyperactivity and emotional lability.
Kayser-Fleischer ring:
- Kayser-Fleischer ring is a green-brown discoloration at the corneal periphery.
- Absence of detection on examination does not exclude the diagnosis of Wilson.
It is an important criterion in diagnosis and disappears with treatment.
> Another important ocular finding is sunflower cataract.
Hemolytic anemia: Coombs test negative hemolytic anemia may be due to the occasional release of copper into the blood. Wilson's disease in association with hemolytic anemia and chronic liver disease, especially in people under the age of 40.
should be considered.
Fanconi syndrome: Copper that is excreted in the urine can accumulate in the kidney tubules and lead to proximal renal tubular damage.
> Skeletal system disease: Osteoporosis, osteomalacia, osteoarthritis can be seen.
cardiomyopathy (rare)
Lab:
• Typically, AST rises more than ALT in these patients.
• Low serum ceruloplasmin level is the best laboratory finding that can be a clue in diagnosis (screening test).
• Serum copper level due to ceruloplasmin is low. As the disease progresses, the level of non-ceruloplasmin copper (free copper) in the serum gradually increases.
• Increased copper excretion in 24-hour urine.
Diagnosis:
• Having 2 of the following criteria is usually sufficient for diagnosis:
positive family history
Kayser-Fleischer ring
Coombs negative hemolytic anemia
Low ceruloplasmin and serum copper
Increased urinary copper excretion
• Increasing the amount of copper per dry weight in liver biopsy or genetic analysis (ATP7B mutation) is a definitive diagnosis method.
Treatment:
• Drugs that decrease copper absorption (zinc) and/or increase its excretion (trientine, D-penicillamine) are used in treatment.
• Zinc or trientine is given primarily in Wilson's patients. Zinc is also preferred in maintenance therapy and prophylactic treatment for asymptomatic cases.
• Penicillamine, a copper binding agent, is not preferred due to its side effects.
• Medical treatment may prevent the progression of the disease, but does not correct the cirrhosis that has already occurred.
• Trientine and penicillamine are not given for those with neurological symptoms (neurological symptoms may increase), zinc is given. Tetrathiomolybdate can be used to preserve neurological functions.
• Liver transplantation may be required if acute liver failure or chronic liver failure due to cirrhosis develops. Transplantation is curative.
