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Pathology - Wilson's disease
Definition: An hereditary disease of copper metabolism resulting in the accumulation of toxic copper levels in the liver and brain. Epidemiology: Rare occurrence. • Although most cases manifest during childhood or young adulthood, the diagnosis should be contemplated as a potential etiology of liver disease at any age. • Both males and females are equally impacted. Genetics: An autosomal recessive condition resulting from mutations in the ATP7B gene, which encodes a copper-transporting ATPase. Approximately 100 distinct mutations have been identified, with the majority of individuals exhibiting compound heterozygosity, meaning they possess two separate mutant alleles.
Pathogenesis • The presence of two mutant ATP7B alleles disrupts normal copper transport, resulting in the accumulation of toxic copper levels in hepatocytes and basal ganglia.
Presentation • The majority of individuals exhibit symptoms in childhood or early adulthood, characterized by chronic liver disease or cirrhosis. • A minority of patients exhibit hepatic failure. • Approximately fifty percent of patients thereafter develop neuropsychiatric symptoms resulting from copper accumulation in the brain, typically following the onset of liver illness.
Macroscopy • At the time of presentation, the majority of patients have advanced disease, and the liver is firm due to significant fibrosis or cirrhosis. Histopathology: Liver biopsies reveal a chronic hepatitis pattern characterized by portal inflammation, dispersed lobular inflammation, and varying degrees of fibrosis, contingent upon the disease stage. The diagnosis is strongly indicated by elevated amounts of stainable copper or copper-associated protein in hepatocytes.
Prognosis • The condition is progressive and culminates in cirrhosis if left untreated. • Continuous administration of metal chelating medicines can avert this progression, if the diagnosis is established promptly. The risk of hepatocellular cancer is minimal.
Definition: An hereditary disease of copper metabolism resulting in the accumulation of toxic copper levels in the liver and brain. Epidemiology: Rare occurrence. • Although most cases manifest during childhood or young adulthood, the diagnosis should be contemplated as a potential etiology of liver disease at any age. • Both males and females are equally impacted. Genetics: An autosomal recessive condition resulting from mutations in the ATP7B gene, which encodes a copper-transporting ATPase. Approximately 100 distinct mutations have been identified, with the majority of individuals exhibiting compound heterozygosity, meaning they possess two separate mutant alleles.
Pathogenesis • The presence of two mutant ATP7B alleles disrupts normal copper transport, resulting in the accumulation of toxic copper levels in hepatocytes and basal ganglia.
Presentation • The majority of individuals exhibit symptoms in childhood or early adulthood, characterized by chronic liver disease or cirrhosis. • A minority of patients exhibit hepatic failure. • Approximately fifty percent of patients thereafter develop neuropsychiatric symptoms resulting from copper accumulation in the brain, typically following the onset of liver illness.
Macroscopy • At the time of presentation, the majority of patients have advanced disease, and the liver is firm due to significant fibrosis or cirrhosis. Histopathology: Liver biopsies reveal a chronic hepatitis pattern characterized by portal inflammation, dispersed lobular inflammation, and varying degrees of fibrosis, contingent upon the disease stage. The diagnosis is strongly indicated by elevated amounts of stainable copper or copper-associated protein in hepatocytes.
Prognosis • The condition is progressive and culminates in cirrhosis if left untreated. • Continuous administration of metal chelating medicines can avert this progression, if the diagnosis is established promptly. The risk of hepatocellular cancer is minimal.
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