R254X Mutation Study of Primary Carnitine Deficiency in Newborn screening
Date Issued
2011
Date
2011
Author(s)
Chen, Nien-I
Abstract
Background：Primary carnitine deficiency (PCD) is an autosomal recessive fatty acid oxidation disease caused by a defect of carnitine transporter across the cell membrane, and then carnitine is excreted through the kidney and intracellular carnitine is deficiency. Tandem mass spectrometry (MS/MS) screening of newborns can detect both asymptomatic newborns and mothers, but the maternal effects may be one of the reasons for false-negative.
Methods：We first used MS/MS to measure free carnitine level in dried blood spots. We elevated the free carnitine cut-offs, and then combined p.R254X molecular analysis as the second tier analysis tool in the newborn screening flow-chart. Because of p.R254X is the most common mutation in Taiwanese newborns. The goal is to improve the detection rates of PCD.
Results：Out of 30,237 newborn, there were 206 samples which free carnitine levels lower than the cut-offs in the initial screening card and the follow-up samples were requested. We found 12 heterozygote of p.R254X, the carrier rate of p.R254X was 1/2,520.Among them, however, only one newborn was confirmed as a case of PCD, whose genotype dose not contain p.R254X. Therefore, the incidence of newborn with PCD in this study is 1/30,237.
Conclusion：The MS/MS is still a reliable method for detecting PCD.PCD is a very serious disease. Although this study failed to enhance the detection rate of this disease, we should continue to make more discoveries and put more efforts in this study.
Subjects
newborn screening
primary carnitine deficiency
free carnitine
maternal effect
OCTN2 gene
p.R254X mutation
Type
thesis
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