In “Novel ALDH5A1 Variants and Genotype: Phenotype Correlation in SSADH Deficiency,” DiBacco et al. identified 7 novel pathogenic ALDH5A1 variants and reported a correlation between age and the presence and severity of epilepsy and obsessive-compulsive disorder among a cohort of 24 patients with ALDH5A1 variants. Siniscalchi et al. hypothesized that these findings could be attributed to the change in the expression of gamma hydroxybutyric acid (GHB) receptors throughout the lifespan and the impact of GHB on both neuronal and astrocyte functions. Pearl et al. agreed that GHB may contribute to epileptogenicity in this patient population but noted that the phenotypic presentation of these variants may also be the result of GABA-glutamine-glutamate cycle dysfunction.