What is Choroideremia?
Choroideremia (CHM) is a rare inherited disorder that causes progressive vision loss, ultimately leading to complete blindness.
Click play for pronunciation
Living with Choroideremia
This picture series shows the progression of a person’s diminished vision as he ages with Choroideremia (CHM).
The first symptom is generally night-blindness, followed by vision loss in the mid-periphery. These “blind spots” appear in an irregular ring, only leaving patches of peripheral vision, while central vision is still maintained. Over time the peripheral vision loss extends in both directions leading to “tunnel vision” and eventually complete loss of sight. Loss of acuity, depth perception, color perception and an increase in the severity of night blindness may also occur during this progression. Both the rate of change and the degree of visual loss are variable among those affected, even within the same family. The disease affects the retina, which is the area at the back of the eye. CHM is considered a rare disease because it only affects an estimated 1 in 50,000 individuals.
Choroideremia is genetically passed through families by an X-linked pattern of inheritance. In this type of inheritance, the gene for Choroideremia is located on the X chromosome. Females have two X chromosomes, but generally, only one of the X chromosomes will carry the defective gene. Because females have a healthy version of the gene on their other X chromosome that produces REP-1, they normally do not suffer the full effects of CHM. In many cases, female carriers suffer mild symptoms of CHM later in life, such as night blindness and glare sensitivity. In rare cases, female carriers even suffer the full effects of CHM. Males have only one X chromosome (paired with one Y chromosome) and are therefore genetically susceptible to inherit X-linked diseases. Males cannot be carriers of X-linked diseases, but they will pass the gene on their X chromosome to their daughters, who then become carriers. Affected males never pass an X-linked disease gene to their sons because fathers pass only the Y chromosome to their sons. Female carriers have a 50 percent chance (or 1 chance in 2) of passing the X-linked disease gene to their daughters, who as a result will become carriers and will have a 50 percent chance of passing the gene to their sons, who would then acquire the disease.
The choroideremia gene product is called REP-1 (for Rab escort protein-1). This protein functions to bring other small proteins (thinking of them as signals) into association with an enzyme that adds 20-carbon long chains to the small signals. These signal proteins can then fit into the lipid membrane that surrounds the cell. The small signals are thought to play a role in allowing nutrients to pass across cells. Imagine that this process occurs constantly at the back of the eye as special nutrients are required to keep the biochemical pathways of vision operating at capacity while our eyes are open. Apparently there is another protein called REP-2 in all cells that allows normal cell function if REP-1 is not present. Scientists suggest that the amount of REP-2 may not be sufficient to allow the normal cell processes to occur in some cells such those of the eye. Unfortunately, the male patient with choroideremia makes a defective REP-1 protein that is rapidly lost from the eye and REP-2 is not able to replace its function. You recall that the gene is on the X chromosome. Males only have one X and so only one copy of the gene that makes the protein. If the gene copy is changed, there is no other normal copy around to mask the effect of not having the normal protein available. Research is trying hard to find ways of getting the cells in the eye to make the normal protein.
At this time, there is no treatment or cure for this disease. However, what we have is hope. In our short history, we have already seen incredible advances made in CHM research. Gene Therapy treatment is now in Clinical Trials. Individuals wishing to participate in these Clinical Trials will need to have their diagnosis of CHM verified with a Genetic Test. The early results from these Clinical Trials have been very positive, and may soon offer individuals the first-ever treatment for CHM. Now, it is no longer a question of if a cure will be developed; it is a question of when! The Choroideremia Research Foundation, Inc. is dedicated to helping researchers find that cure or treatment. By donating to the Foundation, or by becoming an active member, you will help us accomplish our goal of restoring sight to CHMers worldwide!
CHMer Mike McCarthy explains what it is like to live with choroideremia in the video below.