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3-Methylglutaconic aciduria type 3(MGCA3)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: 3-alpha methylglutaconic aciduria type III; 3-methylglutaconic aciduria type III; Costeff optic atrophy syndrome; Costeff syndrome; Iraqi Jewish optic atrophy plus; MGA type III; MGCA3; OPA3, AUTOSOMAL RECESSIVE; OPA3-Related 3-Methylglutaconic Aciduria; Optic atrophy 3; OPTIC ATROPHY 3, AUTOSOMAL RECESSIVE; Optic atrophy infantile with chorea and spastic paraplegia
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Costeff syndrome (297232009); 3-Methylglutaconic aciduria type 3 (297232009)
Gene (location): OPA3 (19q13.32)
OMIM®: 258501
Orphanet: ORPHA67047

Disease characteristics

Excerpted from the GeneReview: OPA3-Related 3-Methylglutaconic Aciduria
OPA3-related 3-methylglutaconic aciduria is characterized by optic atrophy and/or choreoathetoid movement disorder with onset before age ten years. Optic atrophy is associated with progressive, decreased visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. Although most individuals develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable. [from GeneReviews]
Meral Gunay-Aygun  |  Marjan Huizing  |  Yair Anikster   view full author information

Additional descriptions

Type III 3-methylglutaconic aciduria is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased (Anikster et al., 2001). The phenotype is similar to Behr syndrome (210000) and may in some cases represent the same disorder (Sheffer et al., 1992; Lerman-Sagie, 1995).
From GHR
Costeff syndrome is a condition characterized by vision loss, movement problems, and intellectual disability. People with Costeff syndrome have degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. This optic nerve atrophy often begins in infancy or early childhood and results in vision loss that worsens over time. Some affected individuals have rapid and involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).Movement problems in people with Costeff syndrome develop in late childhood and include muscle stiffness (spasticity), impaired muscle coordination (ataxia), and involuntary jerking movements (choreiform movements). As a result of these movement difficulties, individuals with Costeff syndrome may require wheelchair assistance.While some people with Costeff syndrome have intellectual disability that ranges from mild to moderate, many people with this condition have normal intelligence.Costeff syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of the acid does not appear to influence the signs and symptoms of the condition. Costeff syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with Costeff syndrome also have high urine levels of another acid called 3-methylglutaric acid.

Clinical features

3-Methylglutaconic aciduria
MedGen UID:
Concept ID:
Disease or Syndrome
A group of five inherited disorders caused by mutations in the AUH, DNAJC19, OPA3, and TAZ genes. The disorders are characterized by impairment in the function of mitochondria, resulting in the accumulation and excretion of 3-methylglutaconic acid, and the presence of 3-methylglutaric acid in the urine.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV3-Methylglutaconic aciduria type 3
Follow this link to review classifications for 3-Methylglutaconic aciduria type 3 in Orphanet.

Recent clinical studies


Costeff H, Apter N, Elpeleg ON, Prialnic M, Böhles HJ
Brain Dev 1998 Jan;20(1):33-5. PMID: 9533558

Clinical prediction guides

Costeff H, Apter N, Elpeleg ON, Prialnic M, Böhles HJ
Brain Dev 1998 Jan;20(1):33-5. PMID: 9533558
Nystuen A, Costeff H, Elpeleg ON, Apter N, Bonné-Tamir B, Mohrenweiser H, Haider N, Stone EM, Sheffield VC
Hum Mol Genet 1997 Apr;6(4):563-9. PMID: 9097959

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