Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Lu Ding Lu, Putuo Qu, Shanghai, 200062, China.
Neonatal Screening Center, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shi, Shanghai, 200000, China.
Neurol Sci. 2018 Oct;39(10):1697-1703. doi: 10.1007/s10072-018-3483-2. Epub 2018 Jul 6.
L-2-hydroxyglutaric aciduria is a genetic metabolic disorder. Its clinical features include elevated levels of hydroxyglutaric acid in body fluids and abnormal magnetic resonance imaging (MRI) in the subcortical white matter, which are affected by the accumulation of L-2-hydroxyglutaric acid.
A boy with psychomotor retardation and progressive ataxia accompanied by abnormal brain MRI findings was tested using whole-exome sequencing.
Next-generation sequencing (NGS) revealed two novel compound heterozygous frameshift mutations, c.407 del A (p.K136SfsTer3) and c.699_c700 ins A (p.D234RfsTer42), in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene, leading to premature termination codons and truncated FAD/NAD(P)-binding domain of L2HGDH protein. Further laboratory testing revealed an increase in the 2-hydroxyglutaric acid level in the urine.
The results suggested that NGS could provide clues for identifying patients with abnormal neuroradiological findings in the subcortical white matter.
L-2-羟戊二酸尿症是一种遗传代谢性疾病。其临床特征包括体液中羟戊二酸水平升高和皮质下白质异常磁共振成像（MRI），这受 L-2-羟戊二酸的积累影响。
对一名伴有精神运动迟缓及进行性共济失调，伴有异常脑 MRI 发现的男孩进行全外显子组测序。
下一代测序（NGS）显示 L-2-羟戊二酸脱氢酶（L2HGDH）基因中存在两个新的复合杂合移码突变，c.407delA（p.K136SfsTer3）和 c.699_c700insA（p.D234RfsTer42），导致 L2HGDH 蛋白的提前终止密码子和截断 FAD/NAD（P）结合域。进一步的实验室检测显示尿液中 2-羟戊二酸水平升高。
结果表明，NGS 可以为识别皮质下白质异常神经影像学发现的患者提供线索。
