Choroideremia is a rare inherited disorder that causes gradual vision loss. It affects between 1 in 50,000 and 1 in 100,000 people. However, asymptomatic female carriers may be underreported, suggesting that the actual prevalence could be higher.
Night blindness is usually the first symptom, followed by peripheral vision loss (tunnel vision). Choroideremia symptoms typically begin in childhood, progressing to complete blindness by late adulthood.
Choroideremia is caused by mutations in the CHM gene, which is located on the X chromosome. There’s no cure for this Choroideremia, but ongoing clinical trials aim to slow or reverse the disease progression.
This article further discusses Choroideremia, including its causes, symptoms, and potential gene therapy treatment.
What is Choroideremia?
Choroideremia is a rare disease characterized by the loss of cell layers in the retina. It’s also known as progressive tapetochoroidal dystrophy and choroidal sclerosis.
The retina is the light-sensitive tissue at the back of the eye. Retinal degeneration affects the following layers:
- Photoreceptors. These light-sensing cells (rods and cones) convert light into electrical signals for the brain to process into images.
- Retinal pigment epithelium (RPE). This layer provides support for the photoreceptors.
- Choroid. This area contains blood vessels that supply the other layers.
People with Choroideremia experience progressive vision loss. It begins with impaired night vision (night blindness) and progresses to a loss of peripheral vision. Central vision is usually preserved until later in life.
What are the Symptoms of Choroideremia?
Generally, the first symptom of Choroideremia is night blindness. This begins in late childhood, typically around 10 years of age.
As the disease progresses into adolescence, loss of peripheral vision occurs. Gradually, peripheral vision loss worsens until only a small area of central vision remains (tunnel vision).
Progressive vision loss continues throughout adulthood. The disease progression rate and severity of vision loss differ from person to person. This is true even among members of the same family.
Over the course of a few decades, visual loss extends to depth perception, color perception, and, finally, central vision. Complete blindness usually occurs around 50 to 70 years of age.
People with this disease may also experience posterior subcapsular cataracts and retinal detachment.
Do Females Have Choroideremia Symptoms?
Female carriers generally have no symptoms. However, an eye doctor may detect signs of retinal pigment epithelium degeneration or depigmentation during a fundus exam.
Females may experience mild symptoms — such as visual field loss and night blindness — later in life.
What Causes Choroideremia?
Choroideremia is an X-linked recessive genetic disease. It’s caused by changes (mutations) in a gene located on the X chromosome.
The mutated gene that causes Choroideremia is the CHM gene.
How Is Choroideremia Inherited?
X-linked diseases such as Choroideremia are passed through families by a gene on the X chromosome. A female with only one mutated gene (heterozygous) is called a carrier in X-linked recessive inheritance.
Females have two X chromosomes. Female carriers have a disease gene on only one X chromosome. The other X chromosome has a healthy CHM gene, which prevents them from experiencing severe vision problems.
Female carriers can pass the disease on to their children even if they don’t have symptoms. They can pass it on to sons or daughters.
Affected males can pass it on to their daughters, making them disease carriers. However, male patients cannot pass the disease on to their sons. This is because the altered gene isn’t carried on the Y chromosome.
Why Are Males Primarily Affected?
Males have one X chromosome; it’s paired with one Y chromosome. When males inherit an X-linked disease gene, no healthy copy compensates for it. Therefore, males are more genetically susceptible to X-linked diseases.
What Does the CHM Gene Do?
The CHM gene encodes Rab escort protein-1 (REP-1). This protein plays an essential role in the metabolism of retinal cells.
A mutated CHM gene won’t encode REP-1, preventing normal function in retinal cells and causing them to die. Over time, retinal degeneration leads to visual acuity impairment and vision loss.
Choroideremia Diagnosis
An ophthalmologist will perform a comprehensive eye exam to check for signs of Choroideremia. Genetic testing will distinguish it from similar retinal diseases, such as retinitis pigmentosa.
Tests that help diagnose Choroideremia include:
- Fundus examination. An eye doctor will dilate your pupils to examine the back of your eye and check for signs of a diseased retina.
- Electroretinogram (ERG). This test uses electrodes on your face and eyelid to measure photoreceptors’ response to light stimulus.
- Fluorescein angiography. This involves injecting a special dye into your veins to highlight the blood vessels in your eye.
- Optical coherence tomography (OCT). This noninvasive imaging test creates pictures of the back of the eye.
- Genetic test. Laboratory testing of genetic material from blood, hair, skin, or amniotic fluid (during pregnancy) can confirm the presence of a mutated CHM gene.
Differential Diagnosis
Choroideremia shares similar signs and symptoms with many other inherited retinal dystrophies, including:
- Gyrate atrophy
- Retinitis pigmentosa
- Myopic degeneration
- Usher syndrome type 1
- Thioridazine hydrochloride retinal toxicity
- Kearns-Sayre syndrome (KSS)
- Bietti’s crystalline dystrophy
Genetic testing information will confirm a diagnosis and rule out these other diseases.
Choroideremia Treatment
No effective treatments or cures for this disease have been established. However, recent clinical research has brought hope of developing a successful gene therapy.1 At this time, treatments focus on coping with the disease.
Living With Choroideremia
Managing this disease may include:
- Healthy diet. Including plenty of fresh fruit and leafy green vegetables
- Nutritional supplements. As needed, including antioxidants, vitamins, and omega-3 fatty acids
- Physical activity. To promote ocular health and overall health
- Avoiding UV exposure. Wearing UV-blocking sunglasses outdoors
- Avoiding smoking. A major risk factor for macular degeneration
- Low vision aids. Such as magnifiers and other devices recommended by a low vision specialist
- Genetic counseling. To inform affected individuals and family members about the inherited nature of genetic diseases and help with decision-making
- Other types of counseling. To cope with visual impairments and other issues related to vision loss, such as depression and anxiety
- Surgery. To repair retinal detachment, a common complication of Choroideremia
- Cataract surgery. To remove posterior subcapsular cataracts
Clinical Trials
Multiple clinical trials investigating retinal gene therapy show promising results for future Choroideremia treatments.1-2,4
The trials involve using viruses to carry out the functions of the altered gene. Initial findings indicate an improvement in visual acuity that lasts for several years.
However, gene therapy has its challenges. Some participants experienced significant complications, including retinal overstretching and inflammation. As ongoing clinical trials are completed, more information will be available in the coming years.
Summary
Choroideremia is a rare genetic eye disease that mostly affects males. It causes gradual visual loss, starting with night blindness in childhood. Progressive visual loss leads to tunnel vision and then blindness later in adulthood.
It’s an X-linked genetic disease involving a mutation in the CHM gene. The CHM mutation causes retinal cells to die. The retinal layers affected include the photoreceptors, retinal pigment epithelium, and choroid.
Because females have two X chromosomes, they can have a disease gene on only one chromosome. This makes them asymptomatic carriers. Males have one X and one Y chromosome, making them genetically susceptible to X-linked diseases.
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