Glycine -Acyltransferase Deficiency due to a Homozygous Nonsense Variant in the : A Novel Inborn Error of Metabolism.

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.