We report the case of a 52 year old male with diabetes mellitus and long st
anding evidence of hepatic iron excess. Initially considered to have haemoc
hromatosis, this patient was reevaluated when hepatic iron stores were foun
d to be unaffected by a prolonged course of weekly phlebotomy. The developm
ent of neurological disease prompted diagnostic consideration of acerulopla
sminaemia, which we confirmed by demonstration of a novel frameshift mutati
on in the ceruloplasmin gene. Our inability to resolve the patient's iron o
verload by regular phlebotomy is consistent with recent animal studies indi
cating an essential role for ceruloplasmin in cellular iron efflux. Evaluat
ion of this case underscores the clinical relevance of aceruloplasminaemia
in the differential diagnosis of hepatic iron overload and provides insight
into the pathogenetic mechanisms of hepatocellular iron storage and efflux
.