Inheritance |
X-linked recessive |
Autosomal recessive |
Prevalence |
1/140,000 male births |
Rare |
1/30,000-1/35,000 |
Responsible gene |
ATP7A |
ATP7B |
Gene location |
Xq13.3 |
13q14.3 |
Gene product |
Copper-transporting P-type ATPase (ATP7A) |
Copper-transporting P-type ATPase (ATP7B) |
Expression |
Almost all tissues except liver |
Liver, kidney, placenta, lung, brain, heart,
muscle, pancreas, and intestine. |
Mutations |
No common mutations |
Splice-site mutations, missense mutations |
R778L and H1069Q substitutions are common in
Asian and European patients, respectively. |
Pathogenesis |
Defect of intestinal Cu absorption; reduced
activities of Cu-dependent enzymes |
Partial defect of intestinal Cu absorption;
reduced activities of Cu-dependent enzymes |
Copper toxicosis; defects of biliary Cu
excretion and Cu incorporation into ceruloplasmin in the liver; copper
accumulates in various tissues |
Clinical features |
Severe neurological degeneration, abnormal
hair, hypothermia, and connective tissue disorders |
Connective tissue disorders, gait
abnormalities, muscle hypotonia |
Liver diseases, neurological diseases and
psychiatric manifestations, Kayser-Fleischer rings, hematuria,
arthritis, cardiomyopathy, and pancreatitis |
Laboratory features |
Decreased serum Cu and ceruloplasmin, and
increased Cu concentrations in cultured fibroblasts |
Slightly decreased serum Cu and ceruloplasmin,
increased Cu concentrations in cultured fibroblasts, and exostosis on
occipital bones |
Decreased serum Cu and ceruloplasmin,
increased urinary Cu excretion, and increased liver Cu concentration |
Treatment |
Cu-histidine injections |
|
Chelating agents (e.g., penicillamine,
trientine), zinc and liver transplantation |
Animal models |
Macular and brindled mice |
Blotchy mouse |
Long–Evans Cinnamon (LEC)
rat Toxic milk
mouse |