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D-2-hydroxyglutaric aciduria 2(D2HGA2)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: D2HGA2
Gene (location): IDH2 (15q26.1)
Monarch Initiative: MONDO:0013345
OMIM®: 613657


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 are 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. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I.

L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.

Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood. [from MedlinePlus Genetics]

Clinical features

From HPO
D-2-hydroxyglutaric aciduria
MedGen UID:
Concept ID:
Disease or Syndrome
An increased concentration of 2-hydroxyglutaric acid in the urine.
MedGen UID:
Concept ID:
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
MedGen UID:
Concept ID:
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
Concept ID:
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
MedGen UID:
Concept ID:
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
D-2-hydroxyglutaric acidemia
MedGen UID:
Concept ID:

Professional guidelines


Gibson KM, ten Brink HJ, Schor DS, Kok RM, Bootsma AH, Hoffmann GF, Jakobs C
Pediatr Res 1993 Sep;34(3):277-80. doi: 10.1203/00006450-199309000-00007. PMID: 8134166

Recent clinical studies


Thirumal Kumar D, Jerushah Emerald L, George Priya Doss C, Sneha P, Siva R, Charles Emmanuel Jebaraj W, Zayed H
Metab Brain Dis 2018 Oct;33(5):1699-1710. Epub 2018 Jul 9 doi: 10.1007/s11011-018-0278-3. PMID: 29987523

Clinical prediction guides

Thirumal Kumar D, Jerushah Emerald L, George Priya Doss C, Sneha P, Siva R, Charles Emmanuel Jebaraj W, Zayed H
Metab Brain Dis 2018 Oct;33(5):1699-1710. Epub 2018 Jul 9 doi: 10.1007/s11011-018-0278-3. PMID: 29987523

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