Copper (Cu) metabolism was selectively studied in seven infants with Menke's steely-hair syndrome (SHS). A daily oral regimen of CuSO4 (584 μg Cu/kg) and l-histidine (100 mg/kg) in three infants produced an increase in serum Cu concentrations ranging from 33–95% of normal, but without the formation of ceruloplasmin. Cohn serum protein fractionation after oral Cu/l-histidine loading showed a disproportionate accumulation of Cu in the albumin fraction (V). The electron spin resonance spectrum of fraction V showed a heightened signal for the SHS patients, suggesting that an increased concentration of a radical Cu species is present after oral loading. The Sephadex G-150 chromatographic profile of serum fraction V in SHS did not differ significantly from controls. These results suggest that, in SHS, Cu absorbed in the presence of l-histidine is in an abnormal complex involving albumin, which does not allow for holoceruloplasmin biosynthesis. Cu and ceruloplasmin concentrations in the cord blood specimen of an infant who went on to develop SHS were normal, a finding which may account for the transient period of seemingly normal development after birth in SHS patients. An almost 6-fold difference in mean Cu concentration was observed in SHS fibroblasts compared to controls. Fibroblast Cu concentration was elevated in one of two possible maternal heterozygotes, a finding which may permit diagnosis of the carrier state for some SHS heterozygotes.Speculation
The basic defect in SHS may be an abnormality in an intracellular Cu binding or transport protein, which is present in multiple tissues. This suggestion is supported by data from intestine and skin fibroblasts and may, in part, explain the common failure of simple Cu replenishment to alter the clinical course of SHS.