Non-convulsive Status Epilepticus in L-2-Hydroxyglutaric Aciduria With a Novel L2HGDH Variant: A Case Report

L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder caused by variants in the L2HGDH gene, typically presenting with developmental delay, cognitive impairment, seizures, movement disorders, and progressive ataxia. We report the case of a 29-year-old man with childhood-onset epilepsy and neurodevelopmental impairment who presented with recurrent episodes of behavioral arrest and unresponsiveness. Video electroencephalography demonstrated frequent right temporal electrographic seizures that fulfilled the Salzburg criteria for non-convulsive status epilepticus (NCSE). Brain MRI showed a characteristic pattern of predominantly subcortical and deep white matter abnormalities with bilateral dentate nucleus and basal ganglia involvement, supporting a diagnosis of L2HGA. Biochemical evaluation was atypical, with elevated ethylmalonic and methylsuccinic acids and abnormalities in the acylcarnitine profile. Long-term valproate exposure was considered a potential contributor to these findings. Quantitative L-2-hydroxyglutarate estimation was unavailable. Whole-exome sequencing identified a previously unreported homozygous L2HGDH missense variant, c.191C>A (p.Ala64Asp), currently classified as a variant of uncertain significance (VUS). The variant was absent from the population databases queried, while multiple in silico tools, including REVEL (0.96), AlphaMissense (0.994), and SIFT (0.001), predicted a deleterious effect. This case broadens the recognized seizure phenotype of L2HGA by highlighting NCSE as a potential presentation and illustrates the complementary role of molecular testing when biochemical evaluation is atypical or incomplete.