Choroideremia (alternative spelling: Choroideraemia) is a genetic condition that causes progressive vision loss mostly in men and is due to a 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 two 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.
What are the symptoms of choroideremia?
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, due to rod cell death because of a lack of nourishment from the choroid. Over time, the visual field narrows and progresses to tunnel vision and blindness commonly occurs in late adulthood.
What is the cause of choroideremia and how is it inherited?
Choroideremia is a rare disease, estimated to affect approximately one in 50,000 people, although the exact prevalence in Ireland is currently unknown. Unlike some other retinal degenerations, such as retinitis pigmentosa, cases of choroideremia are due to mutations in just one gene, known as CHM. This gene makes an essential protein called REP-1, which is involved in escorting essential nutrients between cells in the back of the eye. However, about 20% of patients with a clinical diagnosis of Choroideremia have been found not to have a mutation in the CHM gene.
Choroideremia is genetically passed through families by an X-linked pattern of inheritance. The CHM gene is located on the X chromosome. 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 carriers of the condition, but do not generally display the severe symptoms of the disease. In women, one or other of the two X chromosomes is randomly inactivated in every cell. Usually, in female carriers of X-linked disease genes, including CHM, this results in 50% of the retinal cells working on the altered CHM gene and the other 50% working on the normal copy of the CHM gene. These women will have very subtle, if any, symptoms of the disease. Inactivation, however, in some women may be skewed in favour of either the normal or the altered CHM gene copy. If more than 50% of the normal CHM copy is inactivated, the carrier female will have more symptoms. In rare, extreme cases of skewed inactivation the carrier female might be almost as severely affected as a male. Males only have one X chromosome and will become affected by the condition if he receives a faulty copy of the gene. Affected males cannot pass on the disease to their sons, because they pass on their Y chromosome. Men with choroideremia must pass on the disease gene to all of their daughters, who then become carriers of the gene. Click here for more information about inheritance patterns.
If a family member is diagnosed with choroideremia, it is strongly advised that other members of the family also have an eye exam by an eye doctor (ophthalmologist) who is specially trained to detect retinal diseases.
What treatments are available?
Maximising the remaining vision that an individual has is a crucial first step to take, and there are many new low vision aids including telescopic and magnifying lenses. The wide range of assistive technologies for people with visual impairments provides plenty of choice for users at all stages of sight loss, and this technology has also removed many barriers to education and employment.
There are no proven treatments for choroideremia although in recent years there have been momentous leaps made in clinical research and development. Over the past twenty years, researchers have identified the causative CHM gene, explored gene therapy in mouse models of disease and performed necessary safety tests of the treatment. This has culminated in the authorisation of a small gene therapy clinical trial, and more trials are expected in the near future. In these gene therapy trials, the researchers engineer a small, safe virus to deliver the correct version of the CHM gene into the light-sensing photoreceptor cells in the retina. The patient’s retina is first detached and then the virus is injected underneath using a very fine needle. Early results from this trial have been positive, no safety issues have been reported and in some cases, gains in vision have been observed. However, it is still early days, and monitoring of the safety and effectiveness of this treatment will be a priority for the researchers over the coming years. You can read more about this clinical trial here.
Target 5000 is a Fighting Blindness research project which aims to provide genetic testing for the estimated 5,000 people in Ireland who have a inherited retinal condition. The purpose of this project is to provide a precise diagnosis and more detailed information about the nature and inheritance pattern of the condition. This information will be to a national patient registry which will enable patients who are eligible for clinical trials to be identified. Click here for more information about Target 5000 and how you can get involved.
Being diagnosed with a condition causing sight loss can be very difficult. The Fighting Blindness Insight Counselling Service provides a range of supports for people affected by sight loss and their families. Click here for more information about the Insight Counselling Service or contact Insight on 01 674 6496 firstname.lastname@example.org.
Other Useful links
RareConnect.org is an online social network for patients and families. It was created by EURORDIS (European Rare Disease Organisation) and NORD (National Organisation for Rare Disorders) to provide a safe space where individuals and families affected by rare diseases can connect with each other, share vital experiences, and find helpful information and resources. Communities for specific conditions are built in partnership with patient groups who help create, moderate and maintain the forum.