Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies
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(2020) 15:276
RESEARCH
Open Access
Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies Mengyao Dai1,2†, Bing Xiao1,2†, Huiwen Zhang1,2, Jun Ye1,2, Wenjuan Qiu1,2, Hong Zhu2, Lei Wang2, Lili Liang1,2, Xia Zhan1,2, Wenjun Ji1,2, Yu Wang1,2, Yongguo Yu1,2, Xuefan Gu1,2 and Lianshu Han1,2*
Abstract Background: Propionic acidemia (PA) is a serious metabolic disorder, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability and validity of a biochemical strategy in the prenatal diagnosis of PA, we conducted a retrospective study of our 11-year experiences at a single center. Methods: We accumulated data from 78 pregnancies from 58 families referred to our center and provided prenatal diagnosis by directed genetic analysis and/or metabolite measurement using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) of amniotic fluid (AF) samples. Results: Sixty-five unaffected fetuses (83.33%) and 13 affected fetuses (16.67%) were confirmed in our study. The characteristic metabolites including propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio and 2-methylcitric acid (2MCA) level in unaffected and affected groups showed significant differences (P < 0.0001), while the level of 3hydroxypropionic acid (3HPA) showed no significant difference between the two groups (P > 0.05).Of the 78 pregnancies, 24 fetuses were found to have either one causative pathogenic variant or were without genetic information in the proband. Three of these fetuses had elevated AF levels of C3, C3/C2 ratio, and 2MCA and, thus, were determined to be affected, while the remaining fetuses were determined to be unaffected based on a normal AF metabolite profile. Our genetic and biochemical results were highly consistent with postnatal follow-up results on all unaffected fetuses. Conclusions: We conclude that a biochemical approach can serve as a fast and convenient prenatal diagnostic method for pregnancies at an increased risk for PA, which could be used in conjunction with genetic testing for precise prenatal diagnosis of this disorder. In our analysis, the characteristic metabolites C3 level, C3/C2 ratio, and 2MCA level in AF supernatant were dependable biochemical markers for diagnosis, of which the C3/C2 ratio appears to be the most reliable biochemical marker for the prenatal diagnosis of PA. Keywords: Propionic acidemia, Prenatal diagnosis, Amniotic fluid, Metabolite analysis, Propionylcarnitine
* Correspondence: [email protected] † Mengyao Dai and Bing Xiao contributed equally to this work. 1 Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, School of Medicine, Shanghai Jiao Tong University, 1665 KongJiang Road, Shanghai 200092, China 2 Center for Prenatal Diagnosis, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribut
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