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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Costeff syndrome

Reviewed July 2014

What is Costeff syndrome?

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.

How common is Costeff syndrome?

Costeff syndrome affects an estimated 1 in 10,000 individuals in the Iraqi Jewish population, in which at least 40 cases have been described. Outside this population, only a few affected individuals have been identified.

What genes are related to Costeff syndrome?

Mutations in the OPA3 gene cause Costeff syndrome. The OPA3 gene provides instructions for making a protein whose exact function is unknown. The OPA3 protein is found in structures called mitochondria, which are the energy-producing centers of cells. Researchers speculate that the OPA3 protein is involved in regulating the shape of mitochondria.

OPA3 gene mutations that result in Costeff syndrome lead to a loss of OPA3 protein function. Cells without any functional OPA3 protein have abnormally shaped mitochondria. These cells likely have reduced energy production and die sooner than normal, decreasing energy availability in the body's tissues. It is unclear why the optic nerves and the parts of the brain that control movement are particularly affected.

Related Gene(s)

Changes in this gene are associated with Costeff syndrome.

  • OPA3

How do people inherit Costeff syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Costeff syndrome?

These resources address the diagnosis or management of Costeff syndrome and may include treatment providers.

  • Baby's First Test (
  • Gene Review: OPA3-Related 3-Methylglutaconic Aciduria (
  • Genetic Testing Registry: 3-Methylglutaconic aciduria type 3 (
  • MedlinePlus Encyclopedia: Optic Nerve Atrophy (

You might also find information on the diagnosis or management of Costeff syndrome in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about Costeff syndrome?

You may find the following resources about Costeff syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Costeff syndrome?

  • 3-methylglutaconic aciduria type 3
  • 3-methylglutaconic aciduria type III
  • autosomal recessive OPA3
  • autosomal recessive optic atrophy 3
  • Costeff optic atrophy syndrome
  • infantile optic atrophy with chorea and spastic paraplegia
  • Iraqi Jewish optic atrophy plus
  • MGA3
  • MGA, type III
  • OPA3 defect
  • optic atrophy plus syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about Costeff syndrome?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Costeff syndrome?

aciduria ; ataxia ; atrophy ; autosomal ; autosomal recessive ; cell ; chorea ; disability ; gene ; inborn errors of metabolism ; inherited ; involuntary ; metabolism ; mitochondria ; newborn screening ; nystagmus ; optic atrophy ; optic nerve ; paraplegia ; population ; protein ; recessive ; screening ; spasticity ; strabismus ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Anikster Y, Kleta R, Shaag A, Gahl WA, Elpeleg O. Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews. Am J Hum Genet. 2001 Dec;69(6):1218-24. Epub 2001 Oct 19. (
  • Elpeleg ON, Costeff H, Joseph A, Shental Y, Weitz R, Gibson KM. 3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff) syndrome. Dev Med Child Neurol. 1994 Feb;36(2):167-72. (
  • Ho G, Walter JH, Christodoulou J. Costeff optic atrophy syndrome: new clinical case and novel molecular findings. J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S419-23. doi: 10.1007/s10545-008-0981-z. Epub 2008 Nov 7. Review. (
  • Huizing M, Dorward H, Ly L, Klootwijk E, Kleta R, Skovby F, Pei W, Feldman B, Gahl WA, Anikster Y. OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria. Mol Genet Metab. 2010 Jun;100(2):149-54. doi: 10.1016/j.ymgme.2010.03.005. Epub 2010 Mar 16. (
  • Kleta R, Skovby F, Christensen E, Rosenberg T, Gahl WA, Anikster Y. 3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings. Mol Genet Metab. 2002 Jul;76(3):201-6. (
  • Neas K, Bennetts B, Carpenter K, White R, Kirk EP, Wilson M, Kelley R, Baric I, Christodoulou J. OPA3 mutation screening in patients with unexplained 3-methylglutaconic aciduria. J Inherit Metab Dis. 2005;28(4):525-32. (
  • Wortmann SB, Duran M, Anikster Y, Barth PG, Sperl W, Zschocke J, Morava E, Wevers RA. Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. J Inherit Metab Dis. 2013 Nov;36(6):923-8. doi: 10.1007/s10545-012-9580-0. Epub 2013 Jan 8. Review. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: July 2014
Published: February 8, 2016