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

OPA3 defect


Other Names:
MGA3; 3-alpha methylglutaconic aciduria type III; MGA type III; MGA3; 3-alpha methylglutaconic aciduria type III; MGA type III; Optic atrophy plus syndrome; Optic atrophy infantile with chorea and spastic paraplegia; Iraqi Jewish optic atrophy plus; Optic atrophy 3; Costeff syndrome; Costeff optic atrophy syndrome; Autosomal recessive optic atrophy plus syndrome; Autosomal recessive optic atrophy type 3; Infantile optic atrophy with chorea and spastic paraplegia; 3-methylglutaconic aciduria type III See More
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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 67047

Definition
3-methylglutaconic aciduria type III (MGA III) is an organic aciduria characterised by the association of optic atrophy and choreoathetosis with 3-methylglutaconic aciduria.

Epidemiology
The vast majority of reported cases involved the Iraqi-Jewish population, in which the prevalence of the disorder has been estimated at around 1 in 10 000.

Clinical description
Onset of the optic atrophy occurs during infancy with a progressive decrease in visual acuity. The choreoathetoid movement disorder manifests later, usually within the first ten years of life. Other clinical features may include spastic paraparesis, mild ataxia and cognitive deficit, dysarthria, and nystagmus.

Etiology
MGA III is caused by mutations in the OPA3 gene (19q13.2-q13.3). The biological function of the OPA3 gene product remains to be defined but MGA III is hypothesised to be a primary mitochondrial disorder.

Diagnostic methods
Diagnosis may be suspected up on presentation with early-onset optic atrophy and choreoathetosis (particularly in individuals of Iraqi-Jewish origin) and by detection of an elevation in the levels of 3-methylglutaconic and 3-methylglutaric acid in the urine. Diagnosis can be confirmed by detection of mutations in the OPA3 gene.

Differential diagnosis
MGA type III can be distinguished from other forms of MGA (types I, II and IV; see these terms) on the basis of the clinical phenotype and, more specifically, from 3-MGA type I by the absence of an elevation in 3-hydroxyisovaleric acid levels and normal 3-methylglutaconyl-CoA hydratase activity in cultured fibroblasts. The differential diagnosis may also include Behr syndrome (see this term) and cerebral palsy.

Antenatal diagnosis
Prenatal testing is clinically available for affected families through molecular analysis of amniocytes or chorionic villus samples.

Genetic counseling
MGA III is transmitted as an autosomal recessive trait.

Management and treatment
Treatment is symptomatic only and should be managed by a multidisciplinary team.

Prognosis
The long-term prognosis remains unknown: although the disease progresses during childhood, it appears to stabilise during early adulthood.

Visit the Orphanet disease page for more resources.
Last updated: 3/1/2007

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
3-Methylglutaconic aciduria 0003535
Choreoathetosis 0001266
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
30%-79% of people have these symptoms
Ataxia 0001251
Dysarthria
Difficulty articulating speech
0001260
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Spastic paraparesis 0002313
5%-29% of people have these symptoms
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Percent of people who have these symptoms is not available through HPO
Abnormality of extrapyramidal motor function 0002071
Autosomal recessive inheritance 0000007
Babinski sign 0003487
Chorea 0002072
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Hyperreflexia
Increased reflexes
0001347
Optic atrophy 0000648
Reduced visual acuity
Decreased clarity of vision
0007663
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

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

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • 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.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss OPA3 defect. Click on the link to view a sample search on this topic.

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