Choroideremia

Choroideremia (alternative spelling: choroideraemia) is a genetic condition that causes progressive vision loss, mostly in males, and is due to degeneration of the specialised light-sensing photoreceptor cells that line the back of the eye.

The vision loss due to choroideremia gets worse over time, eventually leading to blindness; however the rate of progression can vary between individuals. Choroideremia is likely to be underdiagnosed as its symptoms are quite similar to a number of other retinal conditions such as retinitis pigmentosa. The distinctive appearances at the back of the eye and X-linked inheritance pattern help eye doctors to make the diagnosis.

Symptoms

Choroideremia causes damage to the network of blood vessels behind the retina that are known as the choroid. The choroid supplies oxygen and nutrients to support and nourish the retinal pigment epithelial (RPE) cells and the photoreceptor (rod and cone) cells. One of the earliest symptoms of the condition is difficulty seeing at night time as the rod cells degenerate due to lack of nourishment from the choroid. Over time, the visual field narrows and progresses to tunnel vision; severe visual impairment commonly occurs in late adulthood.

Cause

Choroideremia is most often due to mutations in a gene called CHM. The CHM gene encodes a protein call Rab escort protein 1 (REP1), which is involved in transporting small sacs (vesicles) containing essential substances to different locations within cells. REP1 malfunction can lead to high levels of oxidative stress in retinal cells, ultimately causing their degeneration.

The exact mechanism of degradation of the different parts of the retina in choroideremia is still not fully clear and may differ between individuals. So far, there have been 280 mutations identified in the CHM gene that can result in choroideremia. Most of these mutations result in a non-functional copy of the gene, which results in the production of a protein that doesn’t work properly or a complete lack of protein.

The CHM gene is located on the X chromosome and choroideremia is passed through families in an X-linked inheritance pattern. Females have two X chromosomes, but generally only one of the chromosomes will carry a faulty copy of the gene and the other functioning copy will compensate. Therefore, females are usually asymptomatic carriers of the condition or experience mild symptoms, although in rare cases they may be severely affected. Males only have one X chromosome, so if the CHM gene is faulty there is no second copy to compensate, resulting in choroideremia. More information on inheritance patterns is available in the About Inherited Sight Loss area of the Retina UK website: https://retinauk.org.uk/about-inherited-sight-loss/genetics-and-retinal-health/.

Treatment

There are currently no treatments available for choroideremia but gene therapy clinical trials are well underway. Another approach using a drug called ataluren could potentially be helpful for people with certain types of CHM mutation, and this is currently being explored in animal models of choroideremia.

Visit www.clinicaltrials.gov for up to date clinical trials information. You can also read about possible treatment approaches for retinal disease at https://retinauk.org.uk/research/approaches-to-treatment.

Retina UK is occasionally approached by researchers and companies looking for our help in recruiting participants for studies or patient involvement initiatives, and we can pass on details of opportunities to people on our database who have expressed an interest in these activities and given their consent to be contacted. Anyone who is not already in contact with Retina UK can call 01280 821334 or email info@RetinaUK.org.uk so that we can add them to our database. It is helpful for us to have as much detail about the diagnosis as possible, including genetic diagnosis if available, as some opportunities are condition specific.

More information

The Retina UK Helpline provides information, support and signposting to people affected by inherited sight loss as well as healthcare and education professionals.

Contact 0300 111 4000 (9.30am – 9.30pm Mon to Fri) or Helpline@RetinaUK.org.uk.