Wilson's disease: An inborn error of metabolism with multiple manifestations

Abstract

1. 1. Classification of Wilson's disease as an inborn error of metabolism is supported by a large amount of evidence concerning the hereditary and biochemical aspects of the disease. 2. 2. The primary inherited defect appears to involve copper metabolism and is characterized by defective synthesis of serum ceruloplasmin, low serum copper and increased quantity of albumin-bound copper. An increased accumulation of copper in the liver, brain and other tissues occurs. The urinary excretion of copper is excessive. 3. 3. The effect of estrogens on the serum ceruloplasmin concentration was studied in seven patients. In three patients, in whom the serum ceruloplasmin was the least depressed, administration of estrogens resulted in a rise in the ceruloplasmin levels to normal or greater than normal values; in one additional instance a slight rise was observed. In three patients no significant change in the serum ceruloplasmin level was demonstrable. 4. 4. Accumulation of copper in the kidney in Wilson's disease results in a characteristic renal lesion, similar in many respects to that seen in the Fanconi syndrome. Glycosuria, aminoaciduria, phosphaturia and uricosuria may occur. In addition, an alteration in renal hemodynamics is usually demonstrable. 5. 5. Radiographic examination of the bones and joints in nineteen patients with Wilson's disease revealed abnormal findings in thirteen. Severe osteoarthritis and bone fragmentation were common. More rarely, osteomalacia and spontaneous fractures also were seen. 6. 6. The limitations of the various hypotheses advanced to explain the pathogenesis and the symptomatology of the disease are discussed.