Summary
Copper, zinc, and selenium are essential trace elements serving as cofactors of many important metalloenzymes. Copper and zinc uptake requires specific carriers in the intestine. Selenium absorption occurs in the duodenum via an active transport sodium pump. Copper excretion takes place only in the liver. Copper metabolism is regulated by two closely related ATPases that differ in tissue expression: ATP7A, present in most non-hepatic tissues; and ATP7B, predominantly expressed in liver.
Wilson’s disease, associated to ATP7B defect, shows neuropsychiatric, ocular, and hepatic symptoms, caused by tissue copper overload due to impaired export into the bile.
Menkes disease, a devastating neurocutaneous disorder, and its milder variant occipital horn syndrome (OHS), due to ATP7A defect, cause systemic copper deficiency, impairing copper-dependent enzymes such as lysyl oxidase, tyrosinase, superoxide dismutase, dopamine beta-monooxygenase, and cytocrome oxidase.
Recently, five additional copper metabolism disorders have been described: (1) ATP7A-related distal hereditary neuropathy, due to specific mutations affecting ATP7A trafficking; (2) Huppke-Brendel syndrome, caused by mutations in an acetyl-CoA transporter involved in copper proteins acetylation; (3) CCS deficiency, caused by defect of copper chaperone to SOD; (4) MEDNIK; and (5) MEDNIK-like syndrome, associated with defects in subunits of adaptor protein complex 1, which regulates copper pump trafficking. Aceruloplasminemia, due to mutations in CP, encoding the copper-containing enzyme ceruloplasmin, is discussed in the chapter on iron metabolism.
Zinc is involved in all major metabolic pathways, so its deficiency is highly detrimental. Conversely, high serum zinc is rarely toxic, probably because it binds to albumin and α2-macroglobulin. Acrodermatitis enteropathica, the main inborn error of zinc metabolism, causes a cutaneous disorder associated with diarrhea, infections, and growth retardation. Rarer zinc metabolism disorders are Spondylocheirodysplastic Ehlers-Danlos syndrome, Birk-Landau-Perez syndrome, and Hyperzincemia with Hypercalprotectinemia.
Selenium is involved in antioxidant defenses, immune response, and thyroid function. Two genetic disorders have been associated so far with selenium metabolism.
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Martinelli, D. (2022). Disorders of Copper, Zinc, and Selenium Metabolism. In: Blau, N., Dionisi Vici, C., Ferreira, C.R., Vianey-Saban, C., van Karnebeek, C.D.M. (eds) Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-67727-5_36
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