Diagnosis: Wilson Disease
• Wilson disease (hepatolenticular degeneration) is a familial neurologic and hepatic disease resulting from mutations in the gene ATP7B, which encodes a metal-transporting P-type ATPase that mediates transmembrane transport of copper within hepatocytes.
• Hepatic copper accumulation and liver injury result from absent or reduced function of ATP7B protein in Wilson disease. Liver tissue staining for copper (e.g., rhodanine stain) or copper-binding protein (e.g., orcein stain, Victoria blue stain) is helpful in establishing the diagnosis but may be negative because of the variable distribution of copper overload within the liver.
• Extremely low serum ceruloplasmin level (<50 mg/L or <5 mg/dL) is strong evidence for the diagnosis of Wilson disease, although mildly decreased levels may be seen in other conditions, and a result in the normal range does not preclude the diagnosis.
• The best biochemical evidence of Wilson disease is the hepatic parenchymal copper concentration, which can be obtained by sending to a specialty laboratory a formalin-fixed, paraffin-embedded block of liver tissue that exceeds 3 mg in weight (needle biopsy specimen >3 mm in length—preferably at least 1 cm in length—or a large section of liver from an explant or postmortem specimen; “hepatic copper quantification”). Hepatic copper content greater than or equal to 250 μg/g dry weight is the characteristic diagnostic threshold (normal concentrations, rarely >50 μg/g dry weight).
• Wilson disease has varied histologic presentations. In children, there may be no significant pathology on light microscopy or a few apoptotic bodies and large droplet steatosis; in adolescents and adults, the features may resemble chronic hepatitis with interface hepatitis and periportal Mallory-Denk bodies, with or without cirrhosis. Cirrhosis is usually present when the clinical presentation of Wilson disease is fulminant hepatitis (typically with marked hemolysis).
