Department of Pediatrics, Sami Ulus Children Hospital, Ankara, Turkey.
Metabolism Unit, Sami Ulus Children Hospital, Babur cad. No: 44, Altındağ, Ankara, 06080, Turkey.
Metab Brain Dis. 2021 Aug;36(6):1213-1222. doi: 10.1007/s11011-021-00718-3. Epub 2021 Apr 1.
Nonketotic hyperglycinemia is an autosomal recessive inborn error of glycine metabolism, characterized by deficient activity of the glycine cleavage enzyme system. Classic nonketotic hyperglycinemia is caused by mutations or genomic changes in genes that encode the protein components of the glycine cleavage enzyme system. We aimed to investigate clinical, biochemical, radiological findings and molecular genetic data in ten Turkish patients with classic nonketotic hyperglycinemia. Ten Turkish patients who were diagnosed with classic nonketotic hyperglycinemia in a single center from 2013 to 2019 were included in this study. Their clinical, radiological, electrophysiological and laboratory data were collected retrospectively. Sixty percent of the patients were in neonatal group, while 40 % of the patients were infantile. There were no late-onset patients. 90 % of the patients had the severe form. All patients had developmental delay and seizures. Mortality ratio was 30 % in all groups and 50 % in the neonatal group, while no mortality was seen in infantile group. Median (range) values of cerebrospinal fluid (CSF) glycine levels, plasma glycine levels and CSF/plasma glycine ratios were 148 (15-320) µmol/L, 896 (87-1910) µmol/L, 0.17 (0.09-0.21) respectively. Diffuse hypomyelination and corpus callosum anomaly were the most common cranial MRI findings and multifocal epileptic activity and burst supression pattern were the most common electroencephalographic findings. Six patients had variants in GLDC gene and four in AMT gene; five novel variants including AMT gene deletion were detected. Prognosis was poor and treatment was not effective, especially in the severe form. Classic nonketotic hyperglycinemia causes high morbidity and mortality. Neonatal-onset disease was more common and severe than infantile-onset disease. The ratio of AMT gene variants might be higher in Turkey than other countries. AMT gene deletion also plays a role in the etiology of classic nonketotic hyperglycinemia.
非酮症高甘氨酸血症是一种甘氨酸代谢的常染色体隐性先天性遗传疾病，其特征是甘氨酸裂解酶系统的活性不足。经典型非酮症高甘氨酸血症是由编码甘氨酸裂解酶系统蛋白成分的基因突变或基因组改变引起的。我们旨在研究 10 例土耳其经典型非酮症高甘氨酸血症患者的临床、生化、影像学表现和分子遗传学数据。
本研究纳入了 2013 年至 2019 年在一家单中心被诊断为经典型非酮症高甘氨酸血症的 10 例土耳其患者。回顾性收集了他们的临床、影像学、电生理学和实验室数据。
60%的患者为新生儿组，40%的患者为婴儿组。无迟发型患者。90%的患者为重度。所有患者均有发育迟缓及癫痫发作。所有组的死亡率为 30%，新生儿组为 50%，婴儿组无死亡。脑脊液（CSF）甘氨酸水平、血浆甘氨酸水平和 CSF/血浆甘氨酸比值的中位数（范围）分别为 148（15-320）µmol/L、896（87-1910）µmol/L、0.17（0.09-0.21）。最常见的头颅 MRI 表现为弥漫性脑白质发育不良和胼胝体异常，最常见的脑电图表现为多灶性癫痫活动和爆发抑制模式。6 例患者 GLDC 基因存在变异，4 例 AMT 基因存在变异；发现 5 种新的变异，包括 AMT 基因缺失。预后较差，治疗效果不佳，尤其是在重度疾病中。
经典型非酮症高甘氨酸血症发病率高，死亡率高。新生儿起病较婴儿起病更常见且更严重。在土耳其，AMT 基因突变的比例可能高于其他国家。AMT 基因缺失也在经典型非酮症高甘氨酸血症的发病机制中起作用。
