1个非酮性高甘氨酸血症家系的临床和分子遗传学分析

非酮性高甘氨酸血症(NKH)是一种罕见的先天性遗传代谢性疾病,该文报道1例GLDC基因突变所致NKH的中国患儿,就其临床经过、基因缺陷进行研究。患儿以早发性代谢性脑病以及大田原综合征起病,血、尿串联质谱分析均未见异常,颅脑MRI提示胼胝体发育欠佳,脑电图提示爆发抑制。目标基因捕获下代测序结合多重连接探针扩增发现,患儿存在GLDC基因的母源外显子15 c.1786 CT(p.R596X)杂合无义突变及父源外显子4-15大片段杂合缺失,均为明确致病突变,确诊为NKH。经过促肾上腺皮质激素、托吡酯、右美沙芬治疗后,患儿病情无好转,4月龄死亡。NKH临床表型复杂,可通过代谢筛查以及分子遗传学分析获得确诊。

Clinical and molecular genetic study of nonketotic hyperglycinemia in a Chinese family

Nonketotic hyperglycinemia (NKH) is a rare,inborn error of metabolism.In this case report,a Chinese male infant was diagnosed with NKH caused by GLDC gene mutation.The clinical characteristics and genetic diagnosis were reported.The infant presented with an onset of early metabolic encephalopathy and Ohtahara syndrome.Both blood and urinary levels of metabolites were in the normal range.Brain MRI images indicated a poor development of corpus callosum,and a burst suppression pattern was found in the EEG.Results of target gene sequencing technology combined with multiplex ligation-dependent probe amplification (MLPA) indicated a heterozygous missense mutation of c.1786 C＞T (p.R596X) in maternal exon 15 and a loss of heterozygosity of 4-15 exon gross deletions in patemal GLDC gene.These definite pathogenic mutations confirmed the diagnosis of NKH.The infant's clinical condition was not improved after treatment with adreno-cortico-tropic-hormone,topiramate and dextromethorphan,and he finally died at 4 months of age.Patients with NKH often exhibit complicated clinical phenotypes and are lack of specific symptoms.NKH could be diagnosed by metabolic screening and molecular genetic analysis.