Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye.

objectivesL-2-hydroxyglutaric aciduria (L2HGA) is a hereditary metabolic disorder characterized by the accumulation of L-2-hydroxyglutaric acid in body fluids, particularly in cerebrospinal fluid, which disrupts neuron function in the central nervous system and triggers oxidative stress. It can cause seizures, developmental disorders, and behavioral abnormalities.

methodsThe study retrospectively evaluated the demographic information, initial symptoms, clinical characteristics, cranial magnetic resonance imaging (MRI) findings, and post-treatment biochemical changes of 10 cases diagnosed with L2HGA.

resultsThe study included five paediatric and five adult cases with a molecular diagnosis of L2HGA. The mean age at diagnosis was 10.1 years. Convulsion was identified as the primary presenting symptom in 70 % of cases. We identified intellectual disability in 80 % of our cases. In addition to the classic cranial MRI findings of subcortical white matter involvement, basal ganglia involvement was detected in 60 % of cases. We found that 2-hydroxyglutaric acid levels in urine organic acid analysis were significantly decreased riboflavin and carnitine post-treatment, with a mean decrease of 133.89 ± 101.43 mmol/mol creatinine (p=0.017). The most common missense variant identified in the

conclusionsL2HGA is a rare metabolic disorder that is more common in communities where consanguineous marriages are prevalent. Early diagnosis enables early treatment and protection of the brain from oxidative stress. As more cases are reported publicly, studies on genotype-phenotype relationships will yield more significant findings.