Challenges and dilemmas in pediatric hepatic Wilson’s disease

Abstract

Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly in the liver and brain. The genetic mutations are vast, well reported in the West but poorly documented in developing countries. Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians. Diagnostic scoring systems are not fool-proof. The availability and affordability of chelators in developing countries impact the drug compliance of patients. While D-penicillamine is a potent drug, its side effects lead to drug discontinuation. Trientine is cost-prohibitive in developing countries. There is no single test to assess the adequacy of chelation. Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool. In the presence of cirrhosis, hypersplenism clouds the assessment of myelosuppression of drugs. Similarly, it may be difficult to distinguish disease tubulopathy from drug-induced glomerulonephritis. Neurological worsening due to chelators may appear similar to disease progression. Presentation as fulminant hepatic failure requires rapid workup. There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices. This review addresses the challenges and clinical dilemmas faced at beside in developing countries.

Keywords: Wilson’s disease, Children, Hepatic Wilson disease, D-penicillamine, Trientine, Exchangeable copper

Core Tip: Wilson’s disease is an important and common cause of chronic liver disease among children with multi-organ affection. There are various biochemical parameters that aid in making the diagnosis but are nonetheless fraught with limitations. Treatment is lifelong and it’s important to maintain adequate chelation while monitoring for its adverse effects. It is important to distinguish the adverse effects of chelators from the disease manifestations per se, as the management is diagonally opposite, for example, differentiating D-penicillamine-induced paradoxical neurological worsening from neurological manifestations of Wilson disease. This review discusses these challenges in making a diagnosis and treating pediatric hepatic Wilson’s disease.