National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

2-Hydroxyglutaric aciduria

2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA). The main features of D-2-HGA vary within the different types but, in general, may include delayed development; seizures; weak muscle tone (hypotonia); and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. The different types and subtypes are caused by different gene mutations and are inherited in an autosomal recessive pattern, except for a D-2HGA subtype, known as type II D-2-HGA, which is inherited in an autosomal dominant pattern.[1] There is no cure yet. Treatment depends on the symptoms. Management mainly involves control of seizures when they are present.[2]
Last updated: 4/7/2017
There is still no established treatment. However, for the D,L-2HGA type (combined type) some researches had used either malate or citrate. During malate treatment, urinary malate concentration increased, but beyond that, no effects were observed. In contrast, treatment with citrate led to some good results, but more studies are needed to confirm the effectiveness of this treatment.[3]
Last updated: 4/7/2017

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Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on 2-Hydroxyglutaric aciduria. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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  1. Hydorxyglutaric aciduria. Genetics Home Reference. August, 2013; http://ghr.nlm.nih.gov/condition/2-hydroxyglutaric-aciduria. Accessed 7/22/2015.
  2. D-2-hydroxyglutaric aciduria. Orphanet. May, 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79315.
  3. Mühlhausen C, Salomons GS, Lukacs Z, Struys EA, van der Knaap MS, Ullrich K & Santer R. Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment. J Inherit Metab Dis. September, 2014; 37(5):775-81. http://www.ncbi.nlm.nih.gov/pubmed/24687295. Accessed 7/22/2015.