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

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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.

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Acknowledgments

The authors would like to thank Dr. Jia Jia and Zhang Dian of Shanghai Center for Bioinformation Technology for their help in data analysis.

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Authors and Affiliations

  1. Department of Neurology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, 355 Lu Ding Lu, Putuo Qu, Shanghai, 200062, China

    Yuanfeng Zhang, Chunmei Wang, Kunfang Yang, Simei Wang & Yucai Chen

  2. Neonatal Screening Center, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shi, Shanghai, 200000, China

    Guoli Tian

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  1. Yuanfeng Zhang
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  2. Chunmei Wang
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  3. Kunfang Yang
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  4. Simei Wang
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Corresponding author

Correspondence to Yucai Chen.

Ethics declarations

The study was performed in accordance with the ethical standards of the responsible committee on human studies (institutional and national) and also with the Helsinki Declaration of 1975 (revised in 2000). The ethical approved for the study was obtained from the Regional committee for Medical and Health Research Ethics, Children’s Hospital of Shanghai (Shanghai City, China) (REK 2017R021-F01). The patient’s parents provided informed consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Zhang, Y., Wang, C., Yang, K. et al. A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review. Neurol Sci 39, 1697–1703 (2018). https://doi.org/10.1007/s10072-018-3483-2

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  • DOI: https://doi.org/10.1007/s10072-018-3483-2

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