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Case Reports
. 2018 Sep 14;19(1):167.
doi: 10.1186/s12881-018-0675-9.

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria

Wei Peng  1   2   3 , Xiu-Wei Ma  1   2   3 , Xiao Yang  1   2   3 , Wan-Qiao Zhang  1   2   3 , Lei Yan  1   2   3 , Yong-Xia Wang  1   2   3 , Xin Liu  1   2   3 , Yan Wang  4   5   6 , Zhi-Chun Feng  7   8   9
Affiliations
Case Reports

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria

Wei Peng et al. BMC Med Genet. .

Abstract

Background: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons.

Case presentation: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic.

Conclusion: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.

Keywords: L-2-Hydroxyglutaric aciduria; L2HGDH; Mutation.

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Conflict of interest statement

Ethics approval and consent to participate

Written consent was obtained from the patient’s guardians. The study was performed with the approval of the Ethical Committee of the PLA Army General Hospital and was conducted according to the Declaration of Helsinki.

Consent for Publication

Consent for publication of the case was obtained for the patient’s guardians, including case description, clinical data and images.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The brain magnetic resonance image (MRI) results of the patient (a). T2-weighted image revealed symmetrical, high-signal changes in the subcortical white matter, basal ganglia, and cerebellar dentate nuclei. The lateral ventricular wall showed multiple nodular gray matter heterotopia. The right side of the cerebellar hemisphere and vermis showed dysplasia. Total ion chromatograms (TIC) and the mass spectrum of the patient (b). Results of L2HGDH mutational analysis (c). Arrows indicate mutation sites. The patient had two novel mutations, one of which was a homozygous missense mutation (c.407A > G, p.K136R). The other one was a heterozygous deletion (c.408delG, p.K136SfsX3). His father showed both the heterozygous missense mutation and the heterozygous delete mutation. His mother had the heterozygous missense mutation (c.407 A > G, p.K136R)
Fig. 2
Fig. 2
The predicted structure of the protein of L2HGDH in cartoon (a) and surface mode (b). The FAD/NAD(P)-binding domain was highlighted as orange. The mutation site 136 of the protein was shown in red spheres which was located in the pocket (shown in th black ellipse) of the FAD/NAD(P)-binding domain
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