Mass spectrometry combined with gene analysis for prenatal diagnosis of β-ketothiolase deficiency#br#
XU Feng, HAN Lian-shu, JI Wen-jun, CHEN Ting, ZHAN Xia, YE Jun, GU Xue-fan
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Abstract: Objective To evaluate the method of measuring acylcarnitine and organic acid in amniotic fluid by tandem mass spectrometry and gas chromatography-mass spectrometry for the prenatal diagnosis of β-ketothiolase deficiency (BKD). Methods The clinical characteristics, metabolites spectrum of the tandem mass spectrometry and gas chromatography-mass spectrometry and the genetic analysis in a patient with β-ketothiolase deficiency (BKD) were analyzed. When the mother was pregnant again, she was being carried out the amniocentesis at 17 weeks of gestation. The level of tiglylcarnitine (C5:1) and 3-hydroxyisovlerylcarnitine (C5-OH) were detectd by tandem mass spectrometry. 2-methyl-3-hydroxybutyric acid and methylcrotonyl glycine were detectd by gas chromatography-mass spectrometry. Meanwhile, gene mutation test of the amniotic fluid cells were performed to confirm the diagnosis of the fetus. Results The clinical features of the proband included poor reaction, dyspnea and fatigue, who finally died after an acute onset of metabolic ketoacidosis. When the mother was pregnant for the second time, the amniotic fluids showed normal level of C5:1, C5-OH, 2-methyl-3-hydroxybutyric acid and methylcrotonyl glycine, indicating the fetus was normal. And it has been confirmed normal by blood tandem mass spectrometry and urine gaschromatography-mass spectrometry after birth. When the mother was pregnant for the third time, C5︰1 and 2-methyl-3-hydroxybutyric acid levels were remarkably increased in the amniotic fluids, while C5-OH and methylcrotonyl glycine were normal, indicating BKD most possibly. Mutation analysis of ACAT1 gene was performed in the amniotic fluid cells, illustrating homozygous c.1124A>G (p.N375S) mutation, the same as the BKD proband. Therefore, the fetus was diagnosed with BKD. Conclusion A combined spectrometry measurements of the amniotic fluid with gene mutation analysis is helpful in BKD prenatal diagnosis.
徐烽 韩连书 季文君 等. 质谱技术联合基因分析进行β-酮硫解酶缺乏症的产前诊断[J]. 发育医学电子杂志, 2018, 6(1): 25-29.
XU Feng, HAN Lian-shu, JI Wen-jun, et al. Mass spectrometry combined with gene analysis for prenatal diagnosis of β-ketothiolase deficiency#br#. Journal of Developmental Medicine(Electronic Version), 2018, 6(1): 25-29.
2018, Vol. 6 
