From Neonatal Cholestasis to Progressive Neurological Impairment: A Case of Niemann-Pick Disease Type C

Physiological neonatal jaundice typically resolves within the first two weeks of life. Persistence beyond this period should prompt evaluation for neonatal cholestasis, which may represent the first manifestation of an underlying metabolic disorder. We report a six-year-old boy who presented at two months of age with cholestatic jaundice, hepatosplenomegaly, and elevated transaminases. Initial findings suggested congenital cytomegalovirus infection; however, liver biopsy was nonspecific, and further investigations were negative, leading to a diagnosis of idiopathic giant cell hepatitis. Although jaundice resolved, hepatosplenomegaly persisted. Developmental delay became apparent at three years, followed by progressive neurological impairment, including ataxia, dysphagia, and vertical supranuclear gaze palsy. Biochemical testing revealed elevated oxysterols, and molecular analysis confirmed Niemann-Pick disease type C (NPC) due to pathogenic NPC1 variants. Treatment with miglustat resulted in transient clinical improvement, and the patient was subsequently enrolled in a phase III clinical trial evaluating N-acetyl-L-leucine. Niemann-Pick disease type C should be considered in children with unexplained neonatal cholestasis and progressive neurological deterioration, as early recognition may enable timely diagnosis and access to disease-modifying therapies, potentially improving clinical outcomes.