What are the common clinical presentations of Wilson disease (hepatolenticular degeneration)?
Owing to multiple genetic mutations of the ATP7B gene, the clinical presentations can be highly variable. The hepatic form presents before the age of 18 years and the neuropsychiatric form in early adulthood (age, 20–30 years); a late-onset form also exists. Manifestations include the following:
• Liver disease: abnormal liver-associated enzymes are seen in over 95% of cases. Liver disease is the initial presentation in 50% of cases and can manifest as asymptomatic transient hepatitis to fulminant hepatitis, chronic active hepatitis, and cirrhosis. A clue to Wilson disease as the etiology for fulminant hepatic failure is the disproportionately low level of aminotransferases (usually <1500 μ/L) and the marked increase in bilirubin due to associated hemolytic anemia (Coombs-negative).
• Neuropsychiatric disease: the most common manifestations are varying tremors, rigidity, and dystonia caused by basal ganglion degeneration. Dysarthria, drooling, and gait ataxia are also common. Psychiatric disorders such as mood disturbances, neurosis, hypophonia, and personality changes occur in up to 33% of cases. These manifestations tend to occur later than the hepatic presentation, but abnormal liver transaminases and Kayser–Fleischer rings are invariably seen in these patients.
• Eyes: Kayser–Fleischer rings are caused by granular deposits in Descement membranes; present in 95% of patients with and 50% to 60% of patients without neurologic symptoms.
• Hematologic: Coombs-negative hemolytic anemia.
• Kidneys: tubular dysfunction, Fanconi syndrome.
• Fertility: amenorrhea, infertility.
• Musculoskeletal: osteoarthritis, osteopenia.
