Nasser Samra Nadra, Morani Ilham, Bayan Hino, Bakry Doua, Shaalan Munia, Saadi Hadi, Beni Shrem Sara, Sawaed Alaa, Kok Gautam, Muffels Irena J, Fuchs Sabine A, Shapira-Rootman Mika, Mor-Shaked Hagar, Mandel Hanna
Department of Genetics, Ziv Medical Center, Bar-Ilan University Faculty of Medicine, Safed, Israel.
Department of Pediatrics, Ziv Medical Center, Safed, Israel.
Harefuah. 2023 Jun;162(6):344-351.
Inborn-Errors of Metabolism (IEM) are genetic disorders resulting from mutations in genes encoding proteins involved in biochemical-metabolic pathways. However, some IEMs lack specific biochemical markers. Early incorporation of next-generation-sequencing (NGS) including whole exome sequencing (WES) into the diagnostic algorithm of IEMs herein provided, increases diagnostic accuracy, permits genetic counseling and improves therapeutic options. This is exemplified by diseases affecting aminoacyl-tRNA synthetases (ARSs), enzymes involved in protein translation. Recent studies showed that supplementing amino-acids to cell-culture and patients with ARSs deficiencies resulted in improvement of biochemical and clinical parameters, respectively.
先天性代谢缺陷（IEM）是由参与生物化学代谢途径的蛋白质编码基因突变引起的遗传性疾病。然而，一些IEM缺乏特异性生化标志物。本文提供的将包括全外显子组测序（WES）在内的新一代测序（NGS）早期纳入IEM诊断算法中，提高了诊断准确性，允许进行遗传咨询并改善了治疗选择。这在影响氨酰-tRNA合成酶（ARS）的疾病中得到了体现，ARS是参与蛋白质翻译的酶。最近的研究表明，分别向细胞培养物和患有ARS缺陷的患者补充氨基酸可改善生化和临床参数。
