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

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

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


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, 5aα, 6β trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β, 5aα, 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.

Original languageEnglish
JournalScience translational medicine
Issue number337
StatePublished - May 4 2016


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