Skip to Main Content


Metabolic disease resulting in abnormal MRI findings and psychomotor retardation, hypotonia, and nonneurologic signs.


Incidence is unknown, but approximately 30 cases have been reported. Inheritance is autosomal recessive.


The enzymatic defect causing this progressive neurometabolic disorder has not been found. d-2-Hydroxyglutaric acid is a stereoisomer of l-2-hydroxyglutaric acid and an intermediate in glutamate, 5-aminolevulinic acid, and gamma-aminobutyric acid (GABA) metabolism. Elevated levels of GABA were found in the cerebrospinal fluid of some patients with d-2-hydroxyglutaric aciduria. A mild and a severe phenotype have been reported, with a more variable clinical picture and less consistency seen on MRI findings of the mild phenotype. Regardless of the phenotype, progressive psychomotor degeneration with macrocephaly, epilepsy (hypsarrhythmia), hypotonia, cerebral and/or cerebellar atrophy with cerebellar ataxia, and mental and motor developmental delay can be found. The most consistent MRI findings are enlargement of the lateral ventricles, subependymal cysts, and signs of delayed cerebral maturation. Nonneurologic manifestations include prenatal and postnatal growth retardation, cardiomyopathy, facial anomalies, and episodic vomiting. Inspiratory stridor and apnea were the reasons for tracheotomy in one patient at age 4 months.


Facial anomalies, which may affect the airway management, have been reported in a minority of cases. Anomalies include macrocephaly and microcephaly, micrognathia, prognathia, and midface hypoplasia. Hypertrophic cardiomyopathy and aortic insufficiency have been reported and warrant preoperative investigation. Check serum electrolytes and volemia in case of recurrent vomiting, and perform a rapid-sequence induction if general anesthesia is required.


L-2-Hydroxyglutaric Aciduria: Inborn error of metabolism manifesting as progressive neurodegenerative disorder with psychomotor retardation.

Amiel J, de Lonlay P, Francannet C, et al: Facial anomalies in D-2-hydroxyglutaric aciduria. Am J Med Genet 86:124, 1999.  [PubMed: 10449646]
Nyhan WL, Shelton D, Jakobs C, et al: D-2-hydroxyglutaric aciduria. J Child Neurol 10:137, 1995.  [PubMed: 7782605]
Van der Knaap MS, Jakobs C, Hoffmann GF, et al: D-2-hydroxyglutaric aciduria: Further clinical delineation. J Inherit Metab Dis 22:404, 1999.

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessAnesthesiology Full Site: One-Year Subscription

Connect to the full suite of AccessAnesthesiology content and resources including procedural videos, interactive self-assessment, real-life cases, 20+ textbooks, and more

$995 USD
Buy Now

Pay Per View: Timed Access to all of AccessAnesthesiology

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.