Excess Copper Chelating Therapy for Wilson Disease Induces Anemia and Liver Dysfunction

Abstract

A 37-year-old man was diagnosed with Wilson disease at the age of 14. His first manifestations were neurological. He was treated with trientine for more than 10 years and suffered from anemia and liver dysfunction. Wilson disease is a genetic disorder characterized by accumulation of copper in the body. Excess copper is toxic, but copper is an essential trace element. Copper-binding ceruloplasmin is important for iron metabolism. Excess copper chelating treatment-induced anemia and iron deposition in the liver was suspected. Proper monitoring of copper status is important for the management of Wilson disease.

Cholestatic liver disease masquerading as Wilson disease

“…As seen in our cholestatic patients, serum Cp levels were low at the outset but after treatment levels rose to normal ranges which cannot be explained in WD. In WD, there is decreased Cp formation (lack of incorporation of copper into apoceruloplasmin) and therefore, after chelation therapy with decreasing liver copper content, Cp levels may further decrease if diagnosis is correct [10]. Serum Cp may increase after treatment only with recovering hepatic synthetic function [1].…”

Wilson Disease

“…[21][22][23][24][25][26][27][28][29][30][31] Added to penicillamine, zinc, and triene is ammonium tetrathiomolybdate, 31 a new agent that could be useful in patients with neuropsychiatric presentation because it has not caused the neurologic deterioration occasioned by penicillamine. 41 Liver transplantation is an effective therapy for individuals with progressive cirrhosis who do not respond to chelation therapy, so targeted hepatic gene therapy is theoretically possible. 41 Liver transplantation is an effective therapy for individuals with progressive cirrhosis who do not respond to chelation therapy, so targeted hepatic gene therapy is theoretically possible.…”

“…31 Important for this endeavor are clinical reports of long-term therapy outcomes in various patient populations [23][24][25][26][27][28][29][30][31] and the appreciation that chelation therapy can cause side effects from copper depletion. 41 Characterization of the Wilson ATPase gene prompted recognition of copper-transporting proteins in most organisms, and emphasis now is on developing a systems biology approach to copper metabolism 4 that will be aided by finding copper chaperones, transporters, and a COX17 protein that delivers copper to cytochrome c oxidase in yeast. 8…”

Pathogenesis and management of Wilson disease

“…Food in the gastrointestinal tract inhibits absorption of the drug, therefore, it should be administrated 1 h before or 2 h after the meals. Excess copper depletion induces anemia and hemosiderosis via reducing ceruloplasmin activity . Previously, the use of d ‐penicillamine was reported to worsen neurological manifestations, however, recent study has reported conflicting results .…”

“…In general, adverse effects due to penicillamine use resolve when trientine is substituted for penicillamine. Hemosiderosis and anemia may occur after excess copper chelation . The initial dose is 750–1500 mg/day and maintenance dose is usually 750 or 1000 mg/day.…”