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OPA3-Related 3-Methylglutaconic Aciduria.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2006 Jul 28 [updated 2013 Dec 19].

Author information

National Human Genome Research Institute, Medical Genetics Branch, Section on Human Biochemical Genetics, National Institutes of Health, Bethesda, Maryland
Associate Professor of Pediatrics and Genetics, Institute of Genetic Medicine, Departments of Pediatrics and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland
Head of Metabolic Unit, Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel



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.


The diagnosis of OPA3-related 3-methylglutaconic aciduria is suggested by elevated urinary excretion of 3-methylglutaconate (3-MGC) and 3-methylglutaric acid (3-MGA) and confirmed by identification of biallelic OPA3 pathogenic variants.


Treatment of manifestations: Supportive and often provided by a multidisciplinary team; treatment of visual impairment, spasticity, and movement disorder as in the general population. Agents/circumstances to avoid: Use of tobacco, alcohol, and medications known to impair mitochondrial function.


OPA3-related 3-methylglutaconic aciduria is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if both pathogenic variants have been identified in an affected family member.

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