L-2-Hydroxyglutaric Aciduria Due to the Homozygous Variant c.905C>T in L2HGDH Without Cognitive Deficits or Gait Disturbance: A Case Report.

L-2-hydroxyglutaric aciduria (L2HGA) is a rare, slowly progressive, autosomal recessive neurometabolic disorder caused by mutations in the L2HGDH gene and characterized by psychomotor developmental delay, cognitive impairment, epilepsy, dystonia, cerebellar ataxia, tremor, dysarthria, pyramidal signs, macrocephaly, leukoencephalopathy, and elevated L-2-hydroxyglutaric acid levels. To date, no case has been reported of a patient with L2HGA caused by the c.905C>T variant in L2HGDH presenting with epilepsy, tetraspasticity, tetraataxia, dysarthria, and dysmorphism, but without cognitive impairment or gait disturbance. The patient is a 22-year-old man from Syria with L2HGA, born to consanguineous parents, who presented with rare generalized seizures, mild tetraspasticity, tetraataxia, dysarthria, facial dysmorphism, and unilateral cryptorchism. His psychomotor development was normal. Cerebral MRI at the age of 18 revealed marked leukoencephalopathy, but no atrophy or involvement of the basal ganglia. Surprisingly, he showed no cognitive impairment, gait disturbances, or macrocephaly. He led an independent life as a mechanic and drove his own car. This case broadens the phenotypic spectrum of L2HGA and demonstrates that the c.905C>T variant in the L2HGDH gene can manifest phenotypically with only mild symptoms and without cognitive deficits or gait abnormalities. It also shows that some of these features may not be present in childhood but may develop only during adolescence or adulthood.