Trace element studies in three patients and a fetus with Menkes' disease. Effect of copper therapy

This paper reports the results of a multielement analysis of postmortem samples of Menkes patients, of which one was untreated and two had been treated for various lengths of time with intramuscular injections of copper-EDTA. The findings have been compared with data from a Menkes fetus and from controls. The results confirm that copper accumulates in various tissues and demonstrate a further increase in copper levels as a result of the treatment with copper-EDTA. Although no clinical improvement was observed, the levels of some copper-containing enzymes normalized during the copper-therapy. Furthermore, in agreement with the identification of the copper-binding protein in the kidney as metallothionein, it was found that not only copper, but also zinc, cadmium, and mercury are trapped in this tissue. A low copper concentration in the brain was also found in a Menkes fetus, indicating that brain damage might already have occurred before birth. Speculation Until recently, Menkes' disease was considered to be due to copper deficiency. However, the symptoms are more typical of a storage disease in which copper is irreversibly trapped in some tissues, in particular in the kidneys, by metallothionein. This abnormal storage pattern gives rise to copper deficiency elsewhere in the organism, particularly in the brain where it may cause irreversible damage in the foetus. Parenteral administration of copper does not lead to clinical improvement. The only "therapy" that seems feasible at present is tracing the carriers of the disease and advising abortion when prenatal diagnosis indicates a male fetus carrying the disease.