Spodenkiewicz Marta, Diez-Fernandez Carmen, Rüfenacht Véronique, Gemperle-Britschgi Corinne, Häberle Johannes
Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland.
Biology (Basel). 2016 Oct 19;5(4):40. doi: 10.3390/biology5040040.
Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism-congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i) this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii) early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition.
谷氨酰胺合成酶（GS）是一种胞质酶，可产生谷氨酰胺，谷氨酰胺是人体中含量最丰富的游离氨基酸。谷氨酰胺是各种代谢途径的主要底物，因此是许多器官功能运作的重要因素；因此，由于GS缺陷导致的谷氨酰胺缺乏与正常生命不相容。人类基因（编码GS）的突变可导致一种极其罕见的隐性先天性代谢缺陷——先天性谷氨酰胺合成酶缺乏症。截至目前，该病仅在三名无亲缘关系的患者中被报道，所有患者均患有新生儿期起病的严重癫痫性脑病。这些患者GS缺乏的标志是体液中谷氨酰胺水平降低，并伴有慢性高氨血症。本综述旨在概括三名已知先天性GS缺乏症患者的临床病史，并总结对这些患者进行检查时所做研究的结果。本文旨在使读者相信：（i）这种疾病可能未得到充分诊断，因为代谢物浓度降低未得到应有的关注；（ii）早期发现GS缺乏症可能有助于改善那些可早期用该病所缺乏的代谢物进行治疗的患者的预后。
