Development of a bile acid–based newborn screen for Niemann-Pick disease type C

• DOI: 10.1126/scitranslmed.aaf2326
• Publication Date: 2016-05-04T19:00:18Z
• Authors: Xuntian Jiang; Rohini Sidhu; Laurel Mydock-McG...; 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-K...; Xiaokui Zhang; Janice Reunert; Thorsten Marquardt; Heiko Runz; Roberto Giugliani; Jean E. Schaffer; Daniel S. Ory
• Keywords: Niemann–Pick disease

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