ABSTRACT
Wilson's disease is an autosomal recessive disorder of copper metabolism resulting
from the absence or dysfunction of a copper transporting P-type ATPase encoded on
chromosome 13. This ATPase is expressed in hepatocytes where it is localized to the
trans-Golgi network and transports copper into the secretory pathway for incorporation
into ceruloplasmin and excretion into the bile. Under physiologic circumstances, biliary
excretion represents the sole mechanism for copper excretion, and thus affected individuals
have progressive copper accumulation in the liver. When the capacity for hepatic storage
is exceeded, cell death ensues with copper release into the plasma, hemolysis, and
tissue deposition. Presentation in childhood may include chronic hepatitis, asymptomatic
cirrhosis, or acute liver failure. In young adults, neuropsychiatric symptoms predominate
and include dystonia, tremor, personality changes, and cognitive impairments secondary
to copper accumulation in the central nervous system. The laboratory diagnosis of
Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary
copper content, and elevated hepatic copper concentration. Molecular genetic analysis
is complex as more than 100 unique mutations have been identified and most individuals
are compound heterozygotes. Copper chelation with penicillamine is an effective therapy
in most patients and hepatic transplantation is curative in individuals presenting
with irreversible liver failure. Elucidation of the molecular genetic basis of Wilson's
disease has permitted new insights into the mechanisms of cellular copper homeostasis.
KEYWORD
Wilson's disease - copper - liver
