Benefits and drawbacks of current copper chelators in Wilson disease

Abstract

Background. Wilson disease (WD) is an autosomal-recessive disorder of copper metabolism, caused by mutations in the ATP7B gene, which codes for a membrane-bound copper-binding ATPase. This leads to progressive copper accumulation in the liver, with hepatic injury and subsequent copper release into the blood. Aim. To analyze the efficacy and side-effects of the current copper chelating agents used in treatment of Wilson disease. Material and methods. Retrospective study of 37 adult patients diagnosed with Wilson disease at the Gastroenterology and Neurology Departments of Fundeni Clinical Institute between 2012-2017. Patients were grouped into three categories: (a) those with isolated liver disease, (b) those with isolated neurologic (or psychiatric) involvement and (c) those with both liver and neurologic involvement. Results. There were 54% females (n=20). Mean age at diagnosis was 23 ± 10 years-old. Liver cirrhosis was diagnosed in 54% of cases. Neurologic involvement was described in 65% of patients. Dysarthria was the most common neurologic feature (43%), followed by parkinsonism (41%). D-Penicillamine was used as initial treatment in 89% of patients, but was interrupted in 27% of them (n=9) due to its adverse reactions. Keyser-Fleischer rings were absent in a significant proportion (40%) of patients with neurologic involvement. Both Trientine and D-Penicillamine were associated with improved or stationary liver fibrosis, however results were slightly better for Trientine. D-Penicillamine appeared to be a better option than Trientine in patients with neurologic involvement. Conclusions. Based on our study, we recommend treatment with D-Penicillamine as first-line therapy in patients with neurologic involvement. However, due to the frequent side-effects of D-Penicillamine, Trientine could be considered firstline treatment in patients with isolated hepatic involvement.