The national niemann-pick type c1 disease database: Correlation of lipid profi les, mutations, and biochemical phenotypes

Abstract

Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profi les, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 patients who participated in the National NPC1 Disease Database. Lipid profi les were obtained from 34 patients (39%) in the survey and demonstrated signifi cantly reduced plasma LDL cholesterol (LDL-C) and increased plasma triglycerides in the majority of patients. Reduced plasma HDL cholesterol (HDL-C) was the most consistent lipoprotein abnormality found in male and female NPC1 patients across age groups and occurred independent of changes in plasma triglycerides. A subset of 19 patients for whom the biochemical severity of known NPC1 mutations could be correlated with their lipid profi le showed a strong inverse correlation between plasma HDL-C and severity of the biochemical phenotype. Gene mutations were available for 52 patients (59%) in the survey, including 52 different mutations and fi ve novel mutations (Y628C, P887L, I923V, A1151T, and 3741- 3744delACTC). Together, these fi ndings provide novel information regarding the plasma lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity.-Garver, W. S., D. Jelinek, F. J. Meaney, J. Flynn, K. M. Pettit, G. Shepherd, R. A. Heidenreich, C. M. Walsh Vockley, G. Castro, and G. A. Francis. The National Niemann-Pick Type C1 Disease Database: correlation of lipid profi les, mutations, and biochemical phenotypes. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.