Koenig Mary Kay, Bonnen Penelope E
Department of Pediatrics, University of Texas Health Science Center, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
JIMD Rep. 2019;43:13-17. doi: 10.1007/8904_2018_94. Epub 2018 Feb 27.
Metabolomic profiling is an emerging technology in the clinical setting with immediate diagnostic potential for the population of patients with Inborn Errors of Metabolism. We present the metabolomics profile of two ABAT deficiency patients both pre- and posttreatment with flumazenil. ABAT deficiency, also known as GABA-transaminase deficiency, is caused by recessive mutations in the gene ABAT and leads to encephalopathy of variable severity with hypersomnolence, hypotonia, hypomyelination, and seizures. Through metabolomics screening of multiple patient tissues, we identify 2-pyrrolidinone as a biomarker for GABA that is informative in plasma, urine, and CSF. These data will enable noninvasive diagnostic testing for the population of patients with disorders of GABA metabolism.
代谢组学分析是临床环境中一项新兴技术，对患有先天性代谢缺陷的患者群体具有直接诊断潜力。我们展示了两名接受氟马西尼治疗前后的ABAT缺乏症患者的代谢组学特征。ABAT缺乏症，也称为γ-氨基丁酸转氨酶缺乏症，由ABAT基因的隐性突变引起，会导致严重程度不一的脑病，伴有嗜睡、肌张力减退、髓鞘形成不足和癫痫发作。通过对多名患者组织进行代谢组学筛查，我们确定2-吡咯烷酮是γ-氨基丁酸的生物标志物，在血浆、尿液和脑脊液中均具有信息价值。这些数据将使对γ-氨基丁酸代谢紊乱患者群体进行无创诊断检测成为可能。
