A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review.

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.