Choroideremia is a rare, inherited disorder that causes progressive
loss of vision due to degeneration of the choroid and retina.
What are the symptoms?
Choroideremia, formerly called tapetochoroidal dystrophy, occurs almost
exclusively in males.
In childhood, night blindness is the most common first symptom. As the
disease progresses, there is loss of peripheral vision, causing "tunnel
vision," and later a loss of central vision. Progression of the disease
continues throughout a person's life, although both the rate and the
degree of visual loss can vary, even within the same family.
Vision loss due to choroideremia is caused by degeneration of several
layers of cells that are essential to sight. These layers, which line
the inside of the back of the eye, are the choroid, the retinal pigment
epithelium, and the photoreceptor layer.
The choroid consists of fine blood vessels located between the retina
and the sclera (the white of the eye). Choroidal vessels provide the
retinal pigment epithelium and photoreceptors with required oxygen and
The retinal pigment epithelium (RPE) and the photoreceptors are part of
The RPE is associated closely with the photoreceptors and is needed for
their normal function.
The photoreceptors are responsible for converting light into the
electrical impulses that transfer messages to the brain where "seeing"
The RPE and the choroid initially deteriorate in choroideremia.
Eventually, the photoreceptors break down as well.
As the disease progresses, the clinical appearance of these cell layers
changes in a characteristic manner and more vision is lost.
Is it an inherited disease?
Choroideremia is genetically passed through families by the X-linked
pattern of inheritance. In this type of inheritance, the gene for the
disease is located on the X chromosome. Females have two X chromosomes
and can carry the disease gene on one of their X chromosomes. Because
they have a healthy version of the gene on their other X chromosome,
carrier females typically are not affected by X-linked diseases.
Sometimes, however, when eyes of carrier females are examined, the
retina shows minor signs of the disease.
Males have only one X chromosome (paired with one Y chromosome) and
are, therefore, genetically susceptible to X-linked diseases. Males
affected with an X-linked disease always pass the gene on the 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 male offspring.
Female carriers have a 50 percent chance (1 chance in 2) of passing the
X-linked disease gene to a daughter who, if she receives it, becomes a
carrier, with a 50 percent chance of passing the gene to a son, who
will be affected by the disease.
Are there other related diseases?
Early in the course of the disease, choroideremia could be confused
with X-linked retinitis pigmentosa. Both have symptoms of night
blindness and tunnel vision. However, differences are obvious in a
complete medical eye examination, especially as the disease progresses.
The disease most clinically similar to choroideremia is gyrate atrophy.
It can be distinguished based on its inheritance, as an autosomal
recessive disorder, and its cause is known to be a defect in a gene
unrelated to choroideremia.
The genetic problem in choroideremia
Chromosomes are the bearers of genes.
Genes are pieces of DNA-the genetic material that determines who we
are. Genes "code" for proteins that are required for normal functioning
of the body.
A defective, or mutated, gene will produce a flawed protein or maybe no
protein at all.
Choroideremia is caused by a mutation in a gene on the X chromosome
that codes for an important protein called the Rab escort protein-1
(REP-1). This protein normally shuttles other proteins within cells to
form yet another protein that fits into cell membranes and plays a role
in allowing nutrients to pass within cells.
When REP-1 is missing, REP-2 tries to compensate. In the retina,
unfortunately, REP-2 cannot do the whole job and the result is retinal
degeneration. In summary, choroideremia is caused by a mutation of a
gene on the X chromosome. It affects males. It causes degeneration of
the choroid, RPE, and photoreceptor cells. The gene mutation results in
the failure of cells to make a protein that would allow nutrients to
enter its various parts.
What treatment is available?
The search for a treatment for choroideremia is driven by the discovery
of the REP-1 gene. No treatment is currently available but researchers
funded by the Foundation Fighting Blindness are making important
progress that could lead to accurate diagnosis and gene therapies.
How is gene therapy done?
In gene therapy, a vehicle (referred to as a "vector") is used to
introduce a new gene into cells that contain the defective gene.
Vectors are usually viruses that have been modified to make them safe.
(Viruses are very efficient at entering cells, as we all know from how
easily we catch colds and flu.)