Iron accumulation in the liver of male patients with Wilson's disease

OBJECTIVES: There is accumulating evidence that ceruloplasmin, a copper pro tein with ferroxidase activity, plays an important role in iron metabolism. The genetic disorder, aceruloplasminemia, can lead to tissue storage of ir on as in hemochromatosis. Because most patients with Wilson's disease, a ge netic copper toxicosis, have hypoceruloplasminemia, some could be affected by iron overload. METHODS: Four male patients with Wilson's disease were enrolled in this stu dy of pre- and post-treatment iron metabolism. RESULTS: Pretreatment copper contents of the liver were high in all four ma le patients studied as diagnostic of Wilson's disease. Genetic analysis sup ported their clinical diagnosis of Wilson's disease without a background of hemochromatosis. Pretreatment serum ceruloplasmin levels were < 20 mg/dl i n all four patients. A standard penicillamine treatment for 3-8.5 yr furthe r decreased their serum ceruloplasmin levels. Post-treatment serum ferroxid ase activity was low as was the serum ceruloplasmin protein. Copper content s in the liver decreased after treatment in all subjects. In contrast, nonh eme iron in the liver increased during treatment. Pretreatment liver specim ens were positive for histochemical iron in two patients, and post-treatmen t Specimens were positive in all four patients. In two patients, serum amin otransferase levels rebounded with elevation of serum ferritin concentratio n during the treatment period. Subsequent iron reduction by phlebotomy amel iorated their biochemical liver damage. CONCLUSION: Iron overload related to hypoceruloplasminemia may be clinicall y important, particularly in male patients with Wilson's disease. (C) 2001 by Am. Coll. of Gastroenterology.