Effectiveness of Low Dose D-Penicillamine Therapy in Neurologic Wilson Disease - A Prospective Observational Study

Abstract

Background: Wilson disease is an inherited disorder of copper metabolism that mostly manifests as hepatic and neurologic symptoms. Chelation therapy specially penicillamine is given as first line treatment in children with symptomatic Neurologic Wilson disease. Objective: Objective of the study was to assess the safety & the clinical outcome of treatment with low dose penicillamine in Neurologic Wilson disease. Methods: A longitudinal observational study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, a tertiary care Premier Postgraduate Medical Institution of Bangladesh. Thirty-nine (39) patients of Neurologic Wilson disease who fulfill the inclusion and exclusion criteria were evaluated at In-patient Department of Paediatric Neurology, during the period of January 2015 to December 2019. All study children were treated with low dose penicillamine (Cap Artamin 250 mg) rather with conventional dose penicillamine (Cap Artamin 500 mg or 20 mg/kg/day). Subsequent follow up examination was performed at 2 weeks, 1, 3 and 6 months. Follow up was done by global assessment scoring (GAS) and slit lamp examination to see the clinical improvement after treatment with low dose penicillamine therapy. Results: Total number of studied cases were 39. Mean age was 10.2 ± 3.1 year and male to female ratio was 2:1. Most of the patients (66.67%) were arrived from rural area and 20.51% children had history of consanguineous mating parents. Common presenting features were progressive deterioration of school performance (89.74%), gait disturbance (92.31%), dysarthria (92.31%) and dystonia (82.06%) of our studied children. Ophthalmological manifestations like KF ring (100%) found in all patients. Neuroimaging showed bilateral basal ganglia involvement in (63.63%) children followed by hyperintense signal changes (18.18%) and ventricular dilatation in (18.18%) of cases. Majority of the children (74.36%) were improved with low penicillamine therapy clinically and KF ring disappeared in (5.12%) cases after drug therapy on follow up. Commonest side effects were worsening of neurological symptoms in (25.64%) and rash & thrombocytopenia in (5.1%) cases after penicillamine therapy. Conclusion: About three-fourth children of studied Neurologic Wilson disease showed gradual improvement with low-dose penicillamine therapy. Moreover, one-fourth of cases experienced neurological deterioration, which was lower than previously used high dose penicillamine therapy. Therefore, low dose penicillamine may be beneficial as an initial therapy for Wilson disease with neurological manifestations.