Diagnosis of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) by newborn screening: a feasibility study
Date Issued
2014
Date
2014
Author(s)
Chen, Tsung-Chien
Abstract
Background
Glutaric acidemia type II (GA II), also known as multiple acyl-coenzyme A dehydrogenase deficiency (MADD), is an autosomal recessive disease caused by electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) defects. Currently, the diagnosis of GA II in newborn screening dependent on tandem mass spectrometry analysis but the sensitivity is unknown.
Method
We retrospectively analyzed 296,929 acylcarnitines data of newborn screening results using Tool Runner-GA-II. Score higher than 35 were defined as likely or probably (high risk and low risk) to be GA II. We then analyzed if they have A84T and R99G of ETFDH gene by Taqman single nucleotide polymorphisms (SNP) Genotyping Assays. All positive cases were confirmed by direct sequencing.
Result
Totally 1,103 cases (0.4%) were selected as likely or probably GA II. Six cases were in the likely group included three cases of other fatty acid oxidation defects, and 2 cases of GA II. Fourteen of the 1,091 analyzed cases in the probably groups had A84T mutation (13 heterozygous, 1 homozygous). A84T allele frequency in this study is 1.35%, similar to other studies. The one with A84T homozygous mutation showed normal acylcarnitines at first screening.
Conclusion
Tool Runner – GA-II can identifies fatty acid oxidation defects including some GA II patients. However, it can’t be a solely tool to detect Taiwan newborns with A84T mutation. Further study is necessary to improve the detection rate.
Subjects
多發性醯基輔酶A去氫酶缺乏症
戍二酸血症第二型
新生兒篩檢
脂質儲積型肌肉病變
Type
thesis
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