Yuanfeng Zhang1, Chunmei Wang1, Kunfang Yang1, Simei Wang1, Guoli Tian2, Yucai Chen3. 1. Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Lu Ding Lu, Putuo Qu, Shanghai, 200062, China. 2. Neonatal Screening Center, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shi, Shanghai, 200000, China. 3. Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Lu Ding Lu, Putuo Qu, Shanghai, 200062, China. chenyucaiphd@hotmail.com.
Abstract
OBJECTIVE: 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. METHOD: A boy with psychomotor retardation and progressive ataxia accompanied by abnormal brain MRI findings was tested using whole-exome sequencing. RESULTS: 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. CONCLUSION: The results suggested that NGS could provide clues for identifying patients with abnormal neuroradiological findings in the subcortical white matter.
OBJECTIVE: 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. METHOD: A boy with psychomotor retardation and progressive ataxia accompanied by abnormal brain MRI findings was tested using whole-exome sequencing. RESULTS: 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. CONCLUSION: The results suggested that NGS could provide clues for identifying patients with abnormal neuroradiological findings in the subcortical white matter.
Authors: E V Saifullina; E Yu Zakharova; M V Kurkina; R V Magzhanov; E V Gaisina; E N Zakirova Journal: Zh Nevrol Psikhiatr Im S S Korsakova Date: 2017
Authors: Muhammad Ikram Ullah; Abdul Nasir; Arsalan Ahmad; Gaurav Vijay Harlalka; Wasim Ahmad; Muhammad Jawad Hassan; Emma L Baple; Andrew H Crosby; Barry A Chioza Journal: BMC Med Genet Date: 2018-02-20 Impact factor: 2.103