Hepatic iron overload in aceruloplasminaemia

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 .