Very low plasma copper levels do not automatically imply severe copper deficiency

Abstract

Copper is an essential co-factor for many enzymes, including cytochromes. The vast majority of plasma copper is transported bound to caeruloplasmin; the rest is bound to albumin, transcuprein and copper-aminoacid complexes. Copperhomeostasis is controlled by the liver, which synthesizes the copper storage/ transport protein apocaeruloplasmin, which forms caeruloplasmin on the addition of copper . Low plasma copper concentrations occur in patients with primary copper de¢ciency (Menke’s disease, non-Wilsonian copper movement disorder) or excess copper syndromes (Wilson’s disease), or secondary to disorders such as nephrotic syndrome, remitting acute leukaemia, some childhood iron de¢ciency anaemias or Kwashiorkor. Oliver et al. described two cases of very low plasma copper concentrations, and concluded that these were as a result of severe copper de¢ciency despite adequate daily copper intake. Both of these patients were given approximately 12% more copper, and the plasma copper concentrations remained more or less unchanged approximately 50 days later. After more than 50 further days, one of the patients eventually achieved a ‘satisfactory’ plasma copper concentration, while the other remained eiectively unchanged. However, the changes in the plasma copper concentrations for both patients seem to be strongly associated with the changes in caeruloplasmin concentrations throughout this period. This is in keeping with plasma copper concentrations being dependent on the production of its transport protein apocaeruloplasmin. The relationship between caeruloplasmin and copper has a correlation coe⁄cient of approximately 0.92, and, as a result, the caeruloplasmin concentration should always be kept in mindwhen interpreting plasma copper concentrations. Low plasma caeruloplasmin concentrations are more likely to result from issues relating to protein metabolism than from copper de¢ciency in these patients. Accordingly, the low plasma copper concentrations described are more likely to have been secondary to the low caeruloplasmin concentrations, and, if the latter increased, the total plasma copper concentration also increased. Thus, the real lesson from these two cases is that very low copper concentrations are not necessarily due to copper de¢ciency, and that it is essential to interpret low plasma copper concentrations in the light of the respective caeruloplasmin concentrations.