Menkes disease (MD; McKusick 309400) is an X-linked neurodegenerative disorder secondary to extrahepatic copper accumulation, caused by mutations of the gene encoding for the intracellular copper transporter ATPase alpha polypeptide (ATP7A). The clinical picture is characterized by severe psychomotor retardation, seizures, skin hypopigmentation and abnormal hair. Biochemically, MD patients have reduced serum levels of copper and ceruloplasmin. In some cases, early supplementation with parenteral copper histidinate reduced seizure activity and improved muscle tone and motor activity. Some of the clinical findings of MD have been proposed to be secondary to reduced activities of copper-dependent enzymes (i.e. cytochrome-c-oxidase, lysyl oxidase and dopamine β-hydroxylase). To study oxidative status and effects of copper histidinate therapy, we serially evaluated urinary organic acids in MD patients. We also evaluated respiratory chain enzymes activities in muscle and/or fibroblasts.
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