Development of a Bile Acid-based Newborn Screen for Niemann-Pick Disease Type C

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2016 May 6

PMID 27147587

Citations 54

Authors

Xuntian Jiang

Rohini Sidhu

Laurel Mydock-McGrane

Fong-Fu Hsu

Douglas F Covey

David E Scherrer

Brian Earley

Sarah E Gale

Nicole Y Farhat

Forbes D Porter

Dennis J Dietzen

Joseph J Orsini

Elizabeth Berry-Kravis

Xiaokui Zhang

Janice Reunert

Thorsten Marquardt

Heiko Runz

Roberto Giugliani

Jean E Schaffer

Daniel S Ory

Affiliations

Soon will be listed here.

Abstract

Niemann-Pick disease type C (NPC) is a fatal, neurodegenerative, cholesterol storage disorder. With new therapeutics in clinical trials, it is imperative to improve diagnostics and facilitate early intervention. We used metabolomic profiling to identify potential markers and discovered three unknown bile acids that were increased in plasma from NPC but not control subjects. The bile acids most elevated in the NPC subjects were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol, an oxysterol elevated in NPC. A high-throughput mass spectrometry-based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots. Analysis of dried blood spots from 4992 controls, 134 NPC carriers, and 44 NPC subjects provided 100% sensitivity and specificity in the study samples. Quantification of the bile acid in dried blood spots, therefore, provides the basis for a newborn screen for NPC that is ready for piloting in newborn screening programs.

Citing Articles

Global and Targeted Metabolomics for Revealing Metabolomic Alteration in Niemann-Pick Disease Type C Model Cells.

Watanabe M, Maekawa M, Miyoshi K, Sato T, Sato Y, Kumondai M Metabolites. 2024; 14(10).

PMID: 39452896 PMC: 11509386. DOI: 10.3390/metabo14100515.

Evaluation of the landscape of pharmacodynamic biomarkers in Niemann-Pick Disease Type C (NPC).

Stern S, Crisamore K, Schuck R, Pacanowski M Orphanet J Rare Dis. 2024; 19(1):280.

PMID: 39061081 PMC: 11282650. DOI: 10.1186/s13023-024-03233-7.

Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.

Mishra S, Kell P, Scherrer D, Dietzen D, Vite C, Berry-Kravis E J Lipid Res. 2024; 65(8):100600.

PMID: 39048052 PMC: 11367646. DOI: 10.1016/j.jlr.2024.100600.

Elevated Bile Acid 3β,5α,6β-Trihydroxycholanoyl Glycine in a Subset of Adult Ataxias Including Niemann-Pick Type C.

Motamed-Gorji N, Khalil Y, Gonzalez-Robles C, Khan S, Mills P, Garcia-Moreno H Antioxidants (Basel). 2024; 13(5).

PMID: 38790666 PMC: 11117656. DOI: 10.3390/antiox13050561.

Challenges in the Definitive Diagnosis of Niemann-Pick Type C-Leaky Variants and Alternative Transcripts.

Encarnacao M, Ribeiro I, David H, Coutinho M, Quelhas D, Alves S Genes (Basel). 2023; 14(11).

PMID: 38002933 PMC: 10671040. DOI: 10.3390/genes14111990.

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