Clinical Profile and Management of Wilson Disease in Children at Nawabshah

Abstract

Background: Wilson disease (WD) is a rare autosomal recessive inherited disorder of copper metabolism caused by mutations in the ATP7B gene, leading to impaired biliary copper excretion and excessive accumulation of copper in various organs, particularly the liver, brain, cornea, and kidneys. Progressive copper deposition results in hepatic dysfunction, neuropsychiatric manifestations, and other systemic complications. If left untreated, the disease can lead to liver failure, severe neurological impairment, and death. Wilson disease commonly presents during late childhood or adolescence, although the onset may vary. The clinical spectrum ranges from asymptomatic liver enzyme elevation to acute hepatitis, chronic liver disease, cirrhosis, or fulminant hepatic failure. Neurological manifestations may include tremors, dystonia, dysarthria, behavioral changes, and cognitive decline. Early diagnosis is critical because timely initiation of chelation therapy can halt disease progression and reverse many clinical manifestations. In developing regions, delayed presentation is common due to limited awareness among caregivers and healthcare providers, inadequate screening programs, and restricted access to specialized diagnostic tests such as serum ceruloplasmin estimation, 24-hour urinary copper excretion, slit-lamp examination for Kayser–Fleischer rings, and genetic testing. Consequently, many children present at advanced stages of disease with significant organ damage. Objective: The objective of this study was to evaluate the clinical presentation, laboratory profile, radiological findings, and management outcomes of children diagnosed with Wilson disease at a tertiary care hospital in Nawabshah. The study also aimed to assess the pattern of organ involvement and response to chelation therapy in the local pediatric population. Methods: This descriptive observational study was conducted in the Department of Pediatrics at People University of Medical and Health Sciences hospital in Nawabshah over a period of six months. A total of 40 children diagnosed with Wilson disease were included in the study. Diagnosis was established based on clinical features, reduced serum ceruloplasmin levels, increased urinary copper excretion, presence of Kayser–Fleischer (KF) rings on slit-lamp examination, and supportive imaging findings where indicated. Detailed demographic data including age, gender, and duration of symptoms were recorded. Clinical evaluation focused on hepatic symptoms (jaundice, hepatomegaly, ascites, bleeding tendencies), neurological manifestations (tremors, dystonia, speech difficulty, behavioral changes), and mixed presentations. Laboratory investigations included liver function tests (ALT, AST, bilirubin), serum ceruloplasmin levels, complete blood count, and coagulation profile. Imaging studies such as abdominal ultrasound were performed to assess liver size, texture, and presence of cirrhosis. Neuroimaging (MRI brain) was carried out in patients presenting with neurological symptoms. All patients were initiated on chelation therapy with D-penicillamine along with zinc supplementation where indicated. Patients were followed regularly to assess clinical response, biochemical improvement, and treatment-related adverse effects. Results: The mean age at diagnosis was 10.8 ± 2.6 years, indicating that most children presented in late childhood. Hepatic manifestations were the most common presentation, observed in 55% of patients. These included chronic liver disease, hepatomegaly, jaundice, and features of portal hypertension. Neurological symptoms were present in 35% of cases, including tremors, dystonia, dysarthria, and behavioral disturbances. A mixed presentation involving both hepatic and neurological features was observed in 10% of patients. Kayser–Fleischer (KF) rings were detected in 70% of cases on slit-lamp examination and were more frequently observed in children with neurological involvement. Serum ceruloplasmin levels were reduced in 85% of patients, supporting the diagnosis. Liver function tests were abnormal in the majority of children, particularly those with hepatic manifestations. All patients were started on D-penicillamine therapy as the primary chelating agent. During follow-up, 75% of patients showed significant clinical and biochemical improvement, including reduction in liver enzyme levels and stabilization or improvement of neurological symptoms. A small proportion of patients required dose adjustment due to mild adverse effects. Conclusion: Wilson disease in children at Nawabshah most commonly presents with hepatic manifestations, followed by neurological involvement. Delayed diagnosis remains a concern in resource-limited settings. Early recognition through careful clinical evaluation and appropriate laboratory testing, along with prompt initiation of chelation therapy such as D-penicillamine, significantly improves clinical outcomes and prevents irreversible organ damage. Strengthening awareness and improving diagnostic facilities are essential to ensure timely management of this potentially treatable genetic disorder.