Nourbakhsh Mona, Miryounesi Mohammad, Tale Ali, Karimzadeh Parvaneh, Sadeghi Hossein, Ghasemi Mohammad-Reza, Alipour Nasrin, Pourbakhtyaran Elham, Hooman Nakisa, Razzaghy-Azar Maryam, Nourbakhsh Mitra, Klaas Lil, Schulke Daniel, Sass Jörn Oliver
Aliasghar Clinical Research Development Center, Department of Pediatrics, School of Medicine Iran University of Medical Sciences Tehran Iran.
Department of Medical Genetics, School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran.
JIMD Rep. 2025 Jul 29;66(5):e70032. doi: 10.1002/jmd2.70032. eCollection 2025 Sep.
The enzyme glycine -acyltransferase (GLYAT) plays a crucial role in detoxifying both xenobiotic and endogenous compounds that contain a carboxylic acid group, such as benzoic acid. Data on the impact of human GLYAT on the glycine conjugation pathway is limited and difficult to determine. In this study, we present a 5.7-year-old girl with gross motor delay first noticed at age 5 months and speech delay evident at the time of diagnosis. To the best of our knowledge, no case of GLYAT enzyme deficiency has been reported to date. Whole exome sequencing (WES) identified a homozygous nonsense variant (NM_201648.3: c.322C>T: p.(Q108Ter)) in the that abolished GLYAT activity in vitro. The detected variant was confirmed by Sanger sequencing. The patient was treated with pantothenic acid and a mitochondrial cocktail consisting of coenzyme Q10, vitamins B1, B2, B6, B12, C, folate, and carnitine, together with a low-protein diet, which led to the alleviation of edema and hypotonia and an improvement in her motor function and social interactions. Her serum glycine level was also normalized. This case identifies a novel homozygous nonsense variant in the , leading to glycine -acyltransferase enzyme deficiency and associated developmental delays.
甘氨酸 - 酰基转移酶（GLYAT）在对含有羧酸基团的外源性和内源性化合物（如苯甲酸）进行解毒过程中起着关键作用。关于人类GLYAT对甘氨酸结合途径影响的数据有限且难以确定。在本研究中，我们报告了一名5.7岁女童，其大运动发育迟缓于5个月大时首次被发现，言语发育迟缓在诊断时明显。据我们所知，迄今为止尚未报道过GLYAT酶缺乏的病例。全外显子组测序（WES）在[具体基因名称未给出]中鉴定出一个纯合无义变异（NM_201648.3: c.322C>T: p.(Q108Ter)），该变异在体外消除了GLYAT活性。通过桑格测序确认了检测到的变异。该患者接受了泛酸以及由辅酶Q10、维生素B1、B2、B6、B12、C、叶酸和肉碱组成的线粒体复合制剂治疗，同时采用低蛋白饮食，这导致水肿和肌张力减退得到缓解，运动功能和社交互动有所改善。她的血清甘氨酸水平也恢复正常。该病例在[具体基因名称未给出]中鉴定出一种新的纯合无义变异，导致甘氨酸 - 酰基转移酶缺乏及相关发育迟缓。
