Researchers have developed a bile acid-based test that they believe could help screen for Niemann-Pick disease type C (NPC) in newborns.
The test involves the analysis of dried blood spots used in standard newborn screening tests to detect the presence of one of three previously unknown bile acids that were found to be markedly elevated in NPC patients but not healthy individuals, the team reports.
From the blood spots of 4992 healthy individuals, 134 NPC carriers and 44 NPC patients, the two-tiered test correctly identified the patients from carriers and healthy individuals with 100% sensitivity and specificity.
"Broad implementation of newborn screening for NPC would eliminate the diagnostic delay and shift diagnosis of the disease to the newborn period before the onset of neurological symptoms", note Daniel Ory (Washington University School of Medicine, St Louis, Missouri, USA) and colleagues in Science Translational Medicine.
"Drug intervention and nonpharmacological supportive care during this asymptomatic period have the potential to markedly delay disease progression and extend life."
The researchers used metabolomic profiling to identify potential biomarkers for the disease, focusing on bile acids because the condition is known to alter sterol metabolism. They identified three - 3β,5α,6β-trihydroxycholanic acid (bile acid A) and its glycine (bile acid B) and taurine (bile acid C) conjugates - that were elevated in NPC versus controls samples 41-, 144- and six-fold, respectively.
The two most prominent biomarkers were then measured in 10 NPC and 16 control dried blood spots as possible markers for newborn screening ; bile acid B unambiguously discriminated NPC samples from controls, while bile acid A did so in all but one.
As the more specific marker, bile acid B was the target for the two-tiered newborn screening test. The first-tier screening run returns results in about 2 minutes, allowing more than 500 samples per day to be tested, but a second tier test is necessary for ambiguous results to rule out false positives and this returns results in about 7 minutes.
The researchers note that among the nearly 5000 patients tested to validate a cutoff of 13.5 ng/mL, only one healthy newborn needed to be tested using the second-tier assay to confirm the result.
They also report that bile acid B concentrations were independent of age and severity of disease, making it universally applicable.
The team believes that NPC is an "excellent candidate" for newborn screening because the frequency of 1:100,000 is comparable to that of five other lysosomal storage disorders currently screened for and at least twice as frequent as many other commonly screened metabolic disorders.
"Moreover, as with other [lysosomal storage disorders], it is anticipated that neonatal screening will reduce long-term morbidity, and the screening and treatment will cost less than long-term care and lost productivity", they say.
By Lucy Piper
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