Vitamin C Treatment in Menkes’ Disease: Failure to Affect Biochemical and Clinical Parameters

Abstract

Menkes’ disease (kinky hair disease, McKusick 30940) is an X-linked recessive disorder characterized by progressive neurological degeneration, hypothermia, seizures, growth retardation, abnormal hair and abnormalities of the major arteries, with death usually within the first 3 years of life (Menkes et al., 1962; Danks et al., 1972). There is an abnormal distribution of copper with low serum, cerebrospinal fluid (CSF), brain and hepatic copper levels but increased copper concentration in kidney, muscle and gut. Cultured fibroblasts show an abnormal accumulation of copper but reduced levels of lysyl oxidase, a copper-containing enzyme (Royce et al., 1980). Decreased activities of other copper-dependent enzymes, such as cytochrome c oxidase, tyrosinase and dopamine-β-hydroxylase, explain many of the clinical symptoms. An abnormal metallothionein gene regulation in response to copper has been found (Leone et al., 1985), but the basic defect has yet to be identified.