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L2HGDH gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

L2HGDH gene

The L2HGDH gene provides instructions for an enzyme that helps produce energy within mitochondria and prevents the toxic buildup of L-2-hydroxyglutarate.

Normal Function

The L2HGDH gene provides instructions for making an enzyme called L-2-hydroxyglutarate dehydrogenase. This enzyme is located in the mitochondria, the energy-producing centers of the cell. It plays a specific role in energy production by converting a compound called L-2-hydroxyglutarate into 2-ketoglutarate, which is then processed by other enzymes to create energy for cellular activities.

Health Conditions Related to Genetic Changes

2-hydroxyglutaric aciduria

More than 70 mutations in the L2HGDH gene have been identified as the cause of L-2-hydroxyglutaric aciduria (L-2-HGA). This condition leads to progressive brain damage beginning early in life.

Genetic changes—such as amino acid substitutions, insertions, or deletions—result in a shortage of functional L-2-hydroxyglutarate dehydrogenase. Without this enzyme, L-2-hydroxyglutarate is not broken down and accumulates to high levels within cells. This buildup is toxic, particularly to brain cells, leading to cell death and the neurological signs and symptoms associated with the disorder.

Frequently Asked Questions

Parents should watch for developmental delays, seizures, or unexplained muscle weakness in infants. If a child shows any of these, a clinician may order a urine organic acid screen or plasma amino acid test to look for elevated L‑2‑hydroxyglutarate, followed by genetic sequencing of the L2HGDH gene. How is L‑2‑hydroxyglutaric aciduria confirmed once a suspicion is raised?::Confirmation typically involves a combination of a positive urine organic acid test showing high L‑2‑hydroxyglutarate, a brain MRI that may reveal characteristic white‑matter changes, and a DNA test that identifies a pathogenic variant in L2HGDH. What dietary or medical interventions can slow the progression of L‑2‑hydroxyglutaric aciduria?::Currently, there is no cure, but some clinicians recommend a low‑protein diet to reduce precursor amino acids, supplementation with antioxidants, and seizure‑control medications. Regular monitoring of metabolic markers and neurodevelopmental assessments helps adjust therapy. Can a carrier parent pass L‑2‑hydroxyglutaric aciduria to their children, and how can they plan for future pregnancies?::L‑2‑hydroxyglutaric aciduria follows an autosomal recessive inheritance pattern. If both parents carry a pathogenic L2HGDH variant, each pregnancy has a 25 % chance of being affected. Genetic counseling and options such as pre‑implantation genetic testing or prenatal diagnosis via chorionic villus sampling can inform family planning.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.