Niemann-Pick disease type C (NPC) is a fatal metabolic disease, due to lack of an enzyme involved in cholesterol metabolism caused. Recently, the University of Washington School of Medicine, led the research team developed a method based on mass spectrometry, can be screened for the disease in newborns. This results of recently published in the journal Science Translational Medicine.
Daniel Ory led team found that compared with normal controls bile acid levels increased in patients with NPC, then devised a method of mass spectrometry to detect dried blood spots of bile acids. The study found that this detection can be highly sensitive and specific distinction between NPC patients and controls.
Niemann-Pick disease type C is an autosomal recessive genetic disease, manifested as excess accumulation of cholesterol in the liver and spleen, and excessive lipid accumulation in the brain. The disease is incurable in the past, but new treatments are in clinical trials. However, NPC diagnosis is often delayed because its early symptoms, so researchers hope to develop a detection before symptoms of the nervous system appear to realize diagnosis and treatment.
Ory and his colleagues focused on the analysis of bile acid, because studies show that bile acids affect sterol metabolism changes by The use of three targeted metabolomics methods, the researchers locked three candidates bile acids, which increase the patient's plasma in NPC1, but no control. Bile acids A and B were increased by 41 and 144-fold increase in bile acid C 6 times.
By combining high-resolution mass spectrometry, hydrogen / deuterium exchange mass spectrometry and high resolution series funky, researchers have attempted to resolve these unknown bile acid structure. Based on their charge to mass ratio of hydrogen / deuterium exchange and possible hydroxyl positions, the researchers propose bile acids A and B are 5 α-cholanic acid-3β, 5α, 6β-triol and 5 α-cholanic acid-3β, 5α , 6β-triol N- (carboxymethyl) -amide. The bile acid is 3β, 5α, 6β bayerite cholestane metabolites.
After confirming these bile acids can be measured by dried blood spots, Ory and colleagues set out to develop a method for detecting to detect dried blood spots in bile acid B. They used two strategies, wherein the first layer is 2.2 minutes using short LC conditions, using a second layer of 7 minutes long LC conditions. In this way, they can be analyzed every day about 500 samples, the method can not distinguish between the first layer after the second layer of analysis.
In order to establish a cut-off value, the researchers analyzed 1013 controls, 130 carriers and dry blood spot samples NPC1 25 NPC1 patients to obtain the reference range for each group. They reported that, 13.5 ng / ml cutoff obtained 100% sensitivity and specificity, only one normal sample need to accept the second layer detection.
"Extensive screening of NPC for newborns would avoid a delay in diagnosis," the authors said. "The drug intervention and support non-drug treatment in non-symptom stage is expected to significantly delay disease progression and prolong life."
没有评论:
发表评论