Ultrastructural identification of iron and copper accumulation in the liver of a male patient with Wilson disease

Abstract

There is accumulating evidence that ceruloplasmin, a copper-containing protein with ferroxidase activity, plays an important role in iron metabolism. Reduction of ferroxidase activity secondary to ceruloplasmin deficiency may induce iron accumulation in various organs as the result of impaired iron transport. A 37-year-old man presented with intention tremor of the right hand. Liver function tests were almost normal, but parameters of trace elements were abnormal: hypocupremia, hypoceruloplaminemia, and hyperferritinemia. Imaging of the abdomen showed a cirrhotic liver with increased density. A diagnosis of the neurological form of Wilson disease was confirmed by copper deposits in the liver obtained by a blind biopsy, and the patient was diagnosed as compound heterozygous for ATP7B mutations. He was treated with 2500 mg/day trientine hydrochloride per os. The second examination was performed after 20 months of treatment. The treatment further reduced serum ceruloplasmin level from 8.9 to less than 4.0 mg/dl. Serum ferroxidase activity was as low as 70 U/l during treatment. Posttreatment liver histology became negative for copper but remained positive for iron. Copper X-rays from hepatocyte lysosomes were no longer detected, but the iron X-ray was still very high post treatment. Thus, microanalysis confirmed compound overload of copper and iron in this male patient with Wilson disease.