Niemann-Pick type C disease (NPC; OMIM #257220) is an inborn error of intracellular cholesterol trafficking. It is an autosomal recessive disorder caused predominantly by mutations in NPC1 Although characterized as a progressive neurological disorder, it can also cause cholestasis and liver dysfunction because of intrahepatocyte lipid accumulation. We report a 7-wk-old infant who was admitted with neonatal cholestasis, and who was diagnosed with a novel homozygous stop-gain variant in NPC1 by rapid whole-genome sequencing (WGS). WGS results were obtained 16 d before return of the standard clinical genetic test results and prompted initiation of targeted therapy.
Keywords: abnormal cholesterol homeostasis; clinodactyly of the 5th finger; foam cells with lamellar inclusion bodies; generalized neonatal hypotonia; hepatosplenomegaly; prolonged neonatal jaundice.
© 2017 Hildreth et al.; Published by Cold Spring Harbor Laboratory Press.