Enfermedad de Niemann-Pick tipo C: desde una colestasis neonatal hacia un deterioro neurológico. Variabilidad fenotípica

Abstract

Introduction Niemann-Pick type C is a lysosomal storage disorder caused by a defect in intracellular trafficking of cholesterol. It is a rare disease, usually caused by mutations in NPC1 gene, but in some cases by mutations in NPC2 gene. Usually it is present in the paediatric age with a great variability of clinical manifestations. This disease leads to neurological degeneration with various age-related symptoms. Transient neonatal cholestasis, the appearance of splenomegaly and/or hepatomegaly may occur years before the neurological symptoms. Patients and methods We report 6 cases diagnosed in our unit in the last 20 years. We reviewed the clinical manifestations, neuroradiological findings (MRI) and molecular analysis of all of them. Results The disease began before 6 years of age and 5 cases had liver dysfunction and cholestasis in the neonatal period. Ascites was detected in 2 cases in prenatal period. Five cases have or had splenomegaly. Mutations in NPC1 gene were detected in all of them. Conclusions It is important to understand this disease and the identification of early clinical symptoms to make an early diagnosis, leading to appropriate treatment and avoiding unnecessary tests. Moreover, it is important to suitably advise families and provide them with genetic counselling.