2-Hydroxyglutaric aciduria

2-Hydroxyglutaric aciduria
File:Alpha-hydroxyglutaric acid.png Alpha-Hydroxyglutaric acid
Classification and external resources
Specialty
OMIM	600721 236792613657615182
DiseasesDB	34515 34514
Patient UK	2-Hydroxyglutaric aciduria

2-hydroxyglutaric aciduria is a group of rare neurometabolic disorders characterized by the significantly elevated levels of hydroxyglutaric acid in ones urine. It is either autosomal recessive or autosomal dominant.

Classification

Most forms of 2-Hydroxyglutaric aciduria have an autosomal recessive pattern of inheritance.

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

L-2-hydroxyglutaric aciduria

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.

D-2-hydroxyglutaric aciduria

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).

Combined D-2- and L-2-hydroxyglutaric aciduria

The combined form is characterized by severe early-onset epileptic encephalopathy and absence of developmental progress. It is caused by recessive mutations in SLC25A1 encoding the mitochondrial citrate carrier.

See also

• 2-hydroxyglutarate synthase
• 2-hydroxyglutarate dehydrogenase
• Hydroxyacid-oxoacid transhydrogenase