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.
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.
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.
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.
- 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
- MGA, type III
- OPA3 defect
- optic atrophy plus syndrome
- American Association for Pediatric Ophthalmology and Strabismus: Optic Nerve Atrophy
- Centers for Disease Control and Prevention: Intellectual Disability (PDF)
- Centers for Disease Control and Prevention: Vision Loss (PDF)
- Kennedy Krieger Institute: Movement Disorders
- MalaCards: 3-methylglutaconic aciduria, type iii
- Merck Manual Consumer Version: Overview of Optic Nerve Disorders
- Orphanet: 3-methylglutaconic aciduria type 3
- Scottish Sensory Centre: Optic Atrophy
- University of Michigan Kellogg Eye Center: Optic Atrophy