Available online 2 December 2022, 107529

L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare autosomal recessive disease resulted from the mutated gene L-2- hydroxyglutarate dehydrogenase (L2HGDH). We presented a female case who inherited the disease from her consanguineous relatives and suffered from cognitive impairment, seizure, and ataxia. Using cerebral magnetic resonance imaging (MRI), urine organic acid test, and high-throughput DNA sequencing, a novel homozygous missense mutation was found in the L2HGDH gene, namely c.847 G>A/p. G283R in exon 7. Summarizing the clinical information of the patient with L-2-HGA exhibited to be beneficial for the diagnosis of this rare disease. In summary, the pathogenic missense mutation in the case was reliably confirmed using the bioinformatics analysis.

L-2-hydroxyglutaric aciduria (L-2-HGA) was first described by Duran in 1980 [1]. It is widely accepted that L-2-HGA occurs asymptomatically in childhood and progresses slowly. It is mainly characterized by retardation in psychomotor development, cerebral symptoms, and epilepsy [2]. The association of L-2-HGA with the escalated levels of 2-HG in body fluid, such as plasma, urine and cerebrospinal fluid, was previously confirmed. L-2-HGA is coded by L2HGDH gene, which is located on chromosome

A right-handed female patient who was aged 24 years old was admitted to Lanzhou University Second Hospital (Lanzhou, China) due to cognitive impairment, seizure, and ataxia. The patient was born naturally, and there was no abnormality in the perinatal period. The growth and development period followed normal milestones. At the age of approximately 8 years old, the patient developed dysarthria, hand tremors, progressive imbalance of walking, and falling easily. In addition, her mother noticed

Detailed family and medical history, clinical manifestations, neurological tests, and accessory examinations provided precious information for the diagnosis of the patient in this study. Seizures and a history of developmental regression are the key clinical denominators to diagnose an inherited metabolic disorder in patients with ataxia [6]. High-throughput DNA sequencing in consanguineous families is a good approach to elucidate numerous unknown gene defects in autosomal

In summary, the pathogenic missense mutation in the case was reliably confirmed using the bioinformatics analysis. The novel homozygous missense mutation can be a valuable diagnostic biomarker. The patient is still followed up.

Not applicable.

The patient and her mother provided written informed consent to publish this case report and the involved images. All the data were collected from the Department of Neurology, Lanzhou University Second Hospital. The study was approved by the Ethics Committee of Lanzhou University Second Hospital (Approval No. 2021A-588), and conformed to the principles of the Declaration of Helsinki.

The authors declare that they have no competing interest.

The authors are deeply grateful to the patient and her mother.

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© 2022 Published by Elsevier B.V.