Original Research ARTICLE
New ratios for performance improvement for identifying acyl-CoA dehydrogenase deficiencies in expanded newborn screening: a retrospective study
- 1The Affiliated Suzhou Hospital of Nanjing Medical University, China
Some success in identifying acyl-CoA dehydrogenase (ACAD) deficiencies before they are symptomatic has been achieved through tandem mass spectrometry. However, there has been several challenges that need to be confronted, including excess false positives, the occasional false negatives and indicators selection. To select ideal indicators and evaluate their performance for identifying ACAD deficiencies, data from 352119 newborn babies, containing 20 cases, were used in this retrospective study. A total of three new ratios, C4/C5DC+C6-OH, C8/C14:1, and C14:1/C16-OH, were selected from 43 metabolites. Around 903 ratios derived from pairwise combinations of all metabolites via multivariate logistic regression analysis were used. In the current study, the regression analysis was performed to identify short chain acyl-CoA dehydrogenase (SCAD) deficiency, medium chain acyl-CoA dehydrogenase (MCAD) deficiency, and very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. In both model-building and testing data, the C4/C5DC+C6-OH, C8/C14:1 and C14:1/C16-OH were found to be better indicators for SCAD, MCAD and VLCAD deficiencies, respectively, compared to [C4, (C4, C4/C2)], [C8, (C6, C8, C8/C2, C4DC+C5-OH/C8:1)], and [C14:1, (C14:1, C14:1/C16, C14:1/C2)], respectively. In addition, 22 mutations, including 5 novel mutations and 17 reported mutations, in ACADS, ACADM, and ACADL genes were detected in 20 infants with ACAD deficiency by using high-thorough sequencing based on target capture. The pathogenic mutations of c.1031A > G in ACADS, c.449_452delCTGA in ACADM and c.1349G > A in ACADL were found to be hot spots in Suzhou patients with SCAD, MCAD, and VLCAD, respectively. In conclusion, we had identified three new ratios that could improve the performance for ACAD deficiencies compared to the used indicators. We considered to utilize C4/C5DC+C6-OH, C8/C14:1, and C14:1/C16-OH as primary indicators for SCAD, MCAD, and VLCAD deficiency, respectively, in further expanded newborn screening practice. In addition, the spectrum of mutations in Suzhou population enriches genetic data of Chinese patients with one of ACAD deficiencies.
Keywords: C4/C5DC+C6-OH, C8/C14:1, C14:1/C16-OH, Short chain acyl-CoA dehydrogenase deficiency, Medium chain acyl-CoA dehydrogenase deficiency, ery long chain acyl-CoA dehydrogenase deficiency, Expanded newborn screening
Received: 02 Apr 2019;
Accepted: 06 Aug 2019.
Copyright: © 2019 Wang, Zhang, Gap, Wang, Ma, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Prof. Hong Li, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China, email@example.com
Prof. Benjing Wang, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China, firstname.lastname@example.org