You are rotating on the medical wards and are asked to make a diagnosis in
a 45-year-old man who presents in a coma with no obtainable medical history.
On physical examination, he is hyperpneic but his vital signs are otherwise
normal. You note the following positive physical findings: icterus, hepatomegaly,
asterixis, and, on neurologic examination, a rigid dystonia.You note a discoloration of his fingernails (see below).
Laboratory studies reveal elevated SGOT, SGPT and bilirubin levels and findings
compatible with a mild hemolytic anemia.
DIAGNOSIS: Wilson's disease.
Wilson's disease is due to abnormal functioning of the gene ATP7B. ATP7B encodes
a transmembrane protein ATPase (ATP7B) which is necessary for the incorporation of
copper into caeruloplasmin and into the bile for excretion. Excess accumulation of
copper results in the hepatic, neurological, ophthalmic and psychiatric manifestations
of the disease.
Excess copper deposition in the liver can cause chronic hepatitis, cirrhosis,
and - as is true in the presented case - fulminant hepatic failure. Neurological manifestations
of Wilson's disease can include tremor, choreiform movements, parkinsonism, gait disturbances,
dysarthria, pseudobulbar palsy, rigid dystonia, and seizures. The disease is treated with zinc and a chelating agent such as penicillamine or trientine.
Note the discoloration of the nail plate due to excess accumulation of copper. Other heavy metals can produce a similar appearance.
Kayser-Fleischer ring in a patient with Wilson's disease.
Cited: Ala A., Walker A.P., Ashkan, K., Dooley, J.S., Schilsky M. Wilson's disease. Lancet. 2007; 369: 397-406.
.