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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism.

BACKGROUND: Calprotectin (complex of S100A8 and S100A9) is the major calcium and zinc-binding protein of phagocytes. We report a new syndrome with recurrent infections, inflammation, and hyperzincaemia associated with excessively high plasma concentrations of calprotectin. METHODS: We measured calprotectin in plasma and protein fractions by ELISA assay and zinc by atomic absorption spectrometry. Plasma proteins were fractionated by size exclusion chromatography and electrophoresis. Mass spectra of purified proteins were determined by MALDI-TOFMS. FINDINGS: We assessed five patients, two of whom are related. All patients had much the same biochemical findings of hyperzincaemia (77-200 micromol/L, reference range 11-18 micromol/L) and raised plasma calprotectin concentrations (1.4-6.5 g/L, reference range <1 mg/L). All patients presented with recurrent infections, hepatosplenomegaly, anaemia, and evidence of systemic inflammation. Three patients had cutaneous inflammation and three presented in infancy with severe growth failure. Size exclusion chromatography showed that zinc and calprotectin were associated in a broad fraction with molecular weight range 100-300 kDa. Analysis by electrophoresis and mass spectrometry showed that the patients' protein contained normal S100A8 and S100A9 subunits. INTERPRETATION: Dysregulation of zinc metabolism associated with accumulation in plasma of S100A8 and S100A9 defines a new disease, which encompasses a pathological role for dysregulation of two members of the large S100 protein family.[1]


  1. Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism. Sampson, B., Fagerhol, M.K., Sunderkötter, C., Golden, B.E., Richmond, P., Klein, N., Kovar, I.Z., Beattie, J.H., Wolska-Kusnierz, B., Saito, Y., Roth, J. Lancet (2002) [Pubmed]
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