ESSENTIALS OF DIAGNOSIS
Rare autosomal recessive disorder that usually occurs in persons under age 40.
Excessive deposition of copper in the liver and brain.
Serum ceruloplasmin, the plasma copper-carrying protein, is low.
Urinary excretion of copper and hepatic copper concentration are high.
Wilson disease (hepatolenticular degeneration) is a rare autosomal recessive disorder that usually occurs in persons between 3 and 55 years of age. The worldwide prevalence is generally stated to be about 30 per million population, but the frequency of the allele appears to be greater than implied by this estimate. The condition is characterized by excessive deposition of copper in the liver and brain. The genetic defect, localized to chromosome 13 (ATP7B), has been shown to affect a copper-transporting adenosine triphosphatase in the liver and leads to copper accumulation in the liver and oxidative damage of hepatic mitochondria. Most patients are compound heterozygotes (ie, carry two different mutations). Over 600 mutations in the Wilson disease gene have been identified. The H1069Q mutation accounts for 37–63% of disease alleles in populations of Northern European descent. The major physiologic aberration in Wilson disease is excessive absorption of copper from the small intestine and decreased excretion of copper by the liver, resulting in increased tissue deposition, especially in the liver, brain, cornea, and kidney.
Wilson disease tends to present as liver disease in adolescents (more common in females) and neuropsychiatric disease in young adults (more common in males), but there is great variability, and onset of symptoms after age 40 is more common than previously thought. The diagnosis should always be considered in any child or young adult with hepatitis, splenomegaly with hypersplenism, Coombs-negative hemolytic anemia, portal hypertension, and neurologic or psychiatric abnormalities. Wilson disease should also be considered in persons under 40 years of age with chronic hepatitis or acute liver failure.
Hepatic involvement may range from elevated liver biochemical tests (although the alkaline phosphatase may be low) to cirrhosis and portal hypertension. In patients with acute liver failure (seen much more often in females than males), the diagnosis of Wilson disease is suggested by an alkaline phosphatase (in units/L)-to-total bilirubin (in mg/dL) ratio less than 4 and an AST-to-ALT ratio greater than 2.2. The neurologic manifestations of Wilson disease are related to basal ganglia dysfunction and include an akinetic-rigid syndrome similar to parkinsonism, pseudosclerosis with tremor, ataxia, and a dystonic syndrome. Dysarthria, dysphagia, incoordination, and spasticity are common. Migraines, insomnia, and seizures have been reported. Psychiatric features include behavioral and personality changes and emotional lability and may precede characteristic neurologic features. The risk of depression is increased. The pathognomonic sign of the condition is the brownish or gray-green Kayser-Fleischer ring (eFigure 16–38), which represents fine pigmented granular deposits in Descemet membrane in the cornea (Figure 16–4). The ring is usually most marked at the superior and inferior poles of ...