Table 1.

Characteristics of Inherited Copper Transport Disorders in Humans

Characteristics	Menkes Disease	Occipital Horn Syndrome	Wilson’s Disease
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