We report the case of an 11-y-old boy with a plasma Zn concentration g
reater than 200 mu mol/L, but with symptoms consistent with Zn deficie
ncy. He has had hepatosplenomegaly, rashes, stunted growth (<3rd centi
le), anemia, and impaired immune function since infancy. He also has v
asculitis and osteoporosis. A plasma Zn-binding protein has been separ
ated and characterized by a combination of size exclusion and ion exch
ange chromatography and electrophoretic studies and by immunologic met
hods. Antibodies to the partially purified protein have been raised in
rabbits. Size exclusion chromatography shows that Zn is bound to a pr
otein with a mass 110 000-300 000 kD. Electrophoretic and mass spectro
metry studies suggest that the protein may be composed of several subu
nits. One component of the isolated protein reacts with antiserum to a
lpha(2)- macroglobulin; immunoprecipitation studies confirm that the p
rotein is not alpha(2)-macroglobulin or a histidine-rich glycoprotein.
Kinetic studies of zinc metabolism in the patient and his mother with
stable Zn isotopes show the presence of increased exchangeable Zn, wi
th a rapid flux from plasma to a stable pool. Liver and muscle Zn and
Cu concentrations are raised, but with no abnormal liver histology. Im
munoreactive metallothionein in the liver is increased. We suggest tha
t this boy may suffer from a previously unrecognized inborn error of Z
n metabolism causing symptomatic zinc deficiency.