OPA3-related conditions are a group of conditions caused by variants in the OPA3 gene.
One of these, 3-methylglutaconic aciduria type III (previously called Costeff syndrome) is a condition that affects the mitochondria, which are structures that are essential to supplying energy in cells.
Children with 3-methylglutaconic aciduria type III are born with regular vision, but over time the optic nerve - which carries messages from the eye to the brain - deteriorates and their vision worsens. Motor milestones such as crawling or walking generally happen later than usual and in late childhood many children develop muscle stiffness and reduced coordination. Some children with 3-methylglutaconic aciduria type III will also experience intellectual disability, though most have normal intelligence. Individuals also have an excess of a substance called 3-methylglutaconic acid present in their urine.
Treatment is focussed on managing an indivudal's symptoms, and some people benefit from wheelchair assistance to alleviate muscle stiffness and coordination problems.
Some variants in the OPA3 gene cause a condition called autosomal dominant optic atrophy and cataract (ADOAC), where inheriting only one gene variant is enough to cause the condition. Symptoms can develop any time from infancy to adulthood and include vision loss due to deterioration of the optic nerve and clouding of the lens (cataracts), as well as problems with movement and coordination.
As humans we have about 23,000 genes. These genes are like tiny instruction manuals that influence our health, growth and development. We inherit half of our genes from our biological mum and the other half from our biological dad. These genes are lined up on structures called chromosomes. Most of us have 23 pairs of chromosomes. The first 22 pairs are called autosomes and for the most part - these are the same among men and women. The 23rd pair determine our sex - two X chromosomes for a female and one X and one Y chromosome for males.
OPA3-related conditions (including 3-methylglutaconic aciduria type III/Costeff syndrome) is known as an autosomal recessive condition. For autosomal recessive conditions, if a person has a variation in one copy of their gene, they are a carrier. This means that they are healthy because they also have a working copy of the gene. But, they can still pass their non-working copy to their child.
If the other parent also happens to be a carrier of the same gene, there is a 25% (1 in 4) chance that they both pass this gene variation on to their child — and as such, have a child affected by the disease.
If both parents are carriers of OPA3-related conditions (including 3-methylglutaconic aciduria type III/Costeff syndrome), there's a one in four chance that their children could develop symptoms.
Carrier testing is like a checkup for your genes. It tests to see if you carry a gene variation that could cause a serious genetic disease in your child. Eugene offers an inclusive genetic carrier screening panel that includes OPA3-related conditions (including 3-methylglutaconic aciduria type III/Costeff syndrome), but there's a total 301 conditions that can be tested.
Eugene's carrier test is a clinical grade test that can be done from the comfort of your own home — it's just a saliva test. You're also paired with a genetic counsellor who provides mindful support and guidance every step of the way.Learn more about carrier screening
The biggest benefit of screening for OPA3-related conditions (including 3-methylglutaconic aciduria type III/Costeff syndrome) is that it can help future parents understand their reproductive risk so they can be ready and empowered to make more informed decisions. If neither partner are carriers, it provides reassurance and peace of mind that the risk of having a child with a genetic disease is low.
Since 90% of children that have a recessive genetic disease like OPA3-related conditions (including 3-methylglutaconic aciduria type III/Costeff syndrome) had no previous family history of it, it often feels completely out of the blue for the parents. Getting screened is a way to know this risk in advance, which can help familes manage or even prevent the disease in the first place.