Thewamit Rapeepat, Khongkhatithum Chaiyos, Thampratankul Lunliya, Kamolvisit Wuttichart, Khongkrapan Arthaporn, Wattanasirichaigoon Duangrurdee
Division of Neurology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Medical Genetics and Metabolism, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Front Pediatr. 2023 Aug 8;11:1155035. doi: 10.3389/fped.2023.1155035. eCollection 2023.
Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1-2 deletion in the gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate-related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause.
非酮症高甘氨酸血症（NKH）在大多数情况下是一种致命的先天性代谢缺陷，通常在新生儿期表现为脑病和难治性癫痫发作。报道的与NKH相关的先天性异常包括胼胝体发育不全、马蹄内翻足、腭裂和先天性心脏病。在此，我们报告一名新生儿，其表现为无明显癫痫发作的脑病、脑静脉窦血栓形成和腭裂。脑电图显示爆发抑制模式，这表明病因可能是代谢或遗传紊乱。血浆和脑脊液的氨基酸分析显示甘氨酸升高。全外显子测序在从患者父亲遗传的基因外显子4中鉴定出一个杂合的c.492C＞G；p.Tyr164Ter变异。进一步的长读长全基因组测序揭示了从患者母亲遗传的基因中外显子1-2缺失。额外分析未发现腭裂相关基因的致病变异。腭裂可能是NKH相关的先天性异常。关于脑静脉窦血栓形成，我们发现了该基因的一个杂合变异（p.Arg189Trp），这是泰国新生儿血栓形成倾向的常见原因。一名患有NKH的新生儿可能表现为无癫痫发作的严重脑病。密切随访临床变化以及进一步的下一代测序对于病因不明的新生儿脑病的确切诊断至关重要。
