L-2-hydroxyglutaric aciduria

2-Hydroxyglutaric aciduria
Alpha-Hydroxyglutaric acid
Classification and external resources
OMIM	600721 236792613657615182
DiseasesDB	34515 34514
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2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in ones urine. It is either autosomal recessive or autosomal dominant.

The signs/symptoms of this condition are consistent with the following:

2-hydroxyglutaric aciduria is an organic aciduria, and because of the stereoisomeric property of 2-hydroxyglutarate different variants of this disorder are distinguished:

The L-2 form is more common, severe, and mainly affects the central nervous system. The basal ganglia are affected, and cystic cavitations in the white matter of the brain are common, beginning in infancy. This form is chronic, with early symptoms such as hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.

It is associated with L2HGDH, which encodes L-2-hydroxyglutarate dehydrogenase. L-2-hydroxyglutarate is produced by promiscuous action of malate dehydrogenase on 2-oxoglutarate, and L-2-hydroxyglutarate dehydrogenase is an example of a metabolite repair enzyme that oxidizes L-2-hydroxyglutarate back to 2-oxoglutarate.

The D2 form is rare, with symptoms including macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. It is caused by recessive mutations in D2HGDH (type I) or by dominant gain-of-function mutations in IDH2 (type II).

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