Newborn Screening Test Developed For Deadly Neurological Disorder

A newborn screening test has been introduced that identifies infants with Niemann-Pick disease type C, an often fatal condition in which cholesterol builds up and eventually destroys brain cells.

Although this disease was untreatable in the past, new therapeutics are now in clinical trials, but they are most likely to be effective if treatment is started as early as possible, before neurodegeneration has occurred. Niemann-Pick type C disease (NPC) typically is not diagnosed until at least age two, after neurological symptoms have begun to develop.


A team of collaborating scientists led by those at Washington University School of Medicine (St. Louis, MO, USA) screened more than 5,000 dried blood spot specimens. Of these, 44 were known to be samples from NPC patients; 134 were samples from people who were known carriers; and the remaining 4,992 were control samples from people without the condition. A high-throughput mass spectrometry–based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots.

The teams 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 NPCs. The NPC patients have about thirty fold higher amounts of this bile acid in the blood than healthy individuals. Importantly, levels of this bile acid also could distinguish between patients with NPC and carriers of the disease who show no symptoms. Analysis of dried blood spots from the controls, the NPC carriers, and the NPC subjects provided 100% sensitivity and specificity in the study samples.

Daniel S. Ory, MD, a Professor of Medicine and the senior author of the study said, “These types of tests can be quite automated. If you’re running 500 samples per day, you can test many specimens at once at robotic handling stations that many state laboratory facilities already have. The cost of materials and labor would be on par with current accepted newborn screening tests. Once established, a reasonable estimate of the cost of running these tests would be less than USD 1 per sample.” The study was published on May 4, 2016, in the journal Science Translational Medicine.

Related Links:
Washington University School of Medicine