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.


RESULTS
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.


CONCLUSIONS
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.
Sampson
Barry
B
Department of Clinical Chemistry, Charing Cross Hospital, W6 8RF, London, UK. b.sampson@ic.ac.uk
Fagerhol
Magne K
MK
Sunderkötter
Cord
C
Golden
Barbara E
BE
Richmond
Peter
P
Klein
Nigel
N
Kovar
Ilya Z
IZ
Beattie
John H
JH
Wolska-Kusnierz
Beata
B
Saito
Yoshiaki
Y
Roth
Johannes
J
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D008297:Male; D013577:Syndrome; D015032:Zinc / Q000097:blood / Q000378:metabolism*
D039841:Leukocyte L1 Antigen Complex; D015032:Zinc