L2HGDH

The L2HGDH gene provides instructions for making an enzyme called L-2-hydroxyglutarate dehydrogenase. This gene is active in cells throughout the body, particularly cells in the brain, muscles, and testes. Little is known about the L-2-hydroxyglutarate dehydrogenase enzyme. Researchers believe it participates in reactions that produce energy for cell activities. Specifically, L-2-hydroxyglutarate dehydrogenase converts a compound called L-2-hydroxyglutarate to another compound called alpha-ketoglutarate. A series of additional enzymes further process alpha-ketoglutarate to a form of energy used by cells.

2-hydroxyglutaric aciduria - caused by mutations in the L2HGDH gene

Researchers have identified several L2HGDH mutations that cause L-2-hydroxyglutaric aciduria. Some of these mutations change single protein building blocks (amino acids) in the L-2-hydroxyglutarate dehydrogenase enzyme. Other mutations delete one or more amino acids from this enzyme. These changes probably impair the normal function of L-2-hydroxyglutarate dehydrogenase by affecting how the enzyme folds into a 3-dimensional shape. With a shortage of functional enzyme, L-2-hydroxyglutarate does not break down and accumulates in cells. Researchers believe that this accumulation is toxic and damages brain cells, leading to the signs and symptoms of L-2-hydroxyglutaric aciduria.