L-2-hydroxyglutaric aciduria is usually clinically detected within the first year of life through psychomotor retardation, epileptic attacks, or cerebellar ataxia. Around half of the patients exhibit macrocephaly. Other symptoms are muscular hypotension (usually during the early stage of the disease), extrapyramidal symptoms, abnormal behavior, and spasticity (tending to occur later on in the progression). Overall, the progression of the disease is slow, with most affected individuals reaching adulthood. However, it may eventually lead to the complete loss of motor skills (e.g. loss of the ability to walk) and speech problems.
In addition, L2HGA is associated with various brain tumors such as ependymomas, primitive neuroectodermal tumors, low and high-grade gliomas, medulloblastomas, and oligodendrogliomas. The exact risk of tumors is not yet known.
In laboratory chemical testing, L2HGA is characterized by high levels of L-2-hydroxyglutaric acid in the urine, plasma, and CSF.