Copper Deficiency as Wilson's Disease Overtreatment: A Systematic Review

Background: Treatment of Wilson's disease (WD), an inherited disease characterized by copper overload, is lifelong and there is the possibility that copper deficiency (CD) may occur. We systematically reviewed the literature to describe treatment patterns, symptoms and outcomes associated with CD. Methods: Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, the PubMed database was searched up to 6 April 2023. Results: Across 17 articles, 20 cases of CD were described, most commonly (15 cases) in WD patients treated with zinc salts (ZS), less often on combined chelator and ZS therapy (3 cases), molybdate salts plus ZS (1), or molybdate alone (1). CD symptoms occurred insidiously, including sideroblastic anemia, neutropenia, axonal sensory neuropathy, posterior cord myelopathy and increased ratio of epileptic seizures (or epilepsy). CD diagnosis was based on symptoms and severely reduced urinary copper excretion (<20 & mu;g/24 h [<0.3 & mu;mol/24 h] on ZS, or <100 & mu;g/24 h [<1.6 & mu;mol/24 h] on chelators) with low total serum copper and ceruloplasmin. Conclusions: Awareness of CD and regular monitoring of copper metabolism is needed during WD treatment. Temporary cessation of anti-copper treatment usually reverses serum copper reductions as well as pancytopenia; however, some symptoms, especially neuropathy and myelopathy, may persist.

Automated summary

This systematic review examines the occurrence of copper deficiency (CD) in Wilson's disease (WD) patients during treatment. CD diagnosis is based on symptoms and blood tests, and regular monitoring of copper metabolism is necessary during treatment. Temporary cessation of anti-copper treatment can usually reverse serum copper reductions seen in CD.