Stargardt Disease

Stargardt disease (also known as fundus flavimaculatus and Stargardt macular

dystrophy) is the most common form of inherited juvenile macular degeneration.
Inherited as an autosomal recessive trait, it is a severe form of MD that begins in late
childhood, leading to legal blindness. Stargardt disease is symptomatically similar to
age-related macular degeneration, and it affects approximately one in 10,000 children.

Stargardt disease is usually diagnosed in individuals under the age of twenty, when
decreased central vision is first noticed. It causes a progressive loss of central vision
and, in the early stages, patients may have good visual acuity, but they may
experience difficulty with reading and seeing in dim lighting. Other common
symptoms of Stargardt disease include blurriness and distortion. On examination, the
ophthalmological findings vary significantly with the progression of the disease. In
fundus photos, patients with early Stargardt disease appear to have simple macular
degeneration. Children with the disease typically begin experiencing dark adaptation
problems and central vision loss between six and twelve years of age, but
symptoms may also first appear in adulthood.

As the disease progresses, lipid rich deposits accumulate in the retinal pigment
epithelium (RPE) layer beneath the macula. This "lipofuscin" appears as
yellowish-tinted flecks. The RPE is a layer of cells that lies between the retina and the
choroid, where it serves the purpose of nourishing the photoreceptor cells. In
advanced Stargardt disease, the buildup of lipofuscin causes atrophy of the macula
and the underlying RPE. The progression of vision loss is variable and can start with
a visual acuity of 20/40 and decrease rapidly (especially in children) to 20/200 (legal
blindness). By age 50, approximately 50% of all of those studied in clinical trials had
visual acuities of 20/200 to 20/400. In late stages of this disease, there may also be
color vision impairment.

Stargardt disease is almost always inherited as an autosomal recessive disorder, with

only ten percent of cases resulting from a dominant mode of inheritance. Autosomal
recessive means that both parents are carriers, having one gene for the disease paired
with one normal gene. As a consequence, each of their children has a 25 percent
chance of inheriting the two copies of the Stargardt gene (one from each parent)
needed to cause the disease. Carriers are unaffected because they have only one copy.
At this time, it is impossible to determine who is a carrier for Stargardt disease until
after an affected child is diagnosed.

In 1997, researchers isolated the gene for Stargardt disease. The ABCA4 gene
produces a protein involved in energy transport to and from photoreceptor cells in the
retina. Mutations in the ABCA4 gene, which cause Stargardt disease, produce a
dysfunctional protein that cannot perform its transport function. As a result,
photoreceptor cells degenerate, and vision loss occurs. One of nineteen mutations in
the gene (causing deletions and substitutions of amino acids) has been identified to
cause Stargardt disease. The non-functional ABCA4 protein permits the accumulation
of yellow fatty material to accumulate in the retina. This material causes flecks and,
ultimately, loss of vision. Further research is needed to find out how the mutated
ABCA4 genes affect the biochemistry of the retina and lead to vision loss.

This discovery allows researchers to study the underlying biochemical interactions

that result from mutations in this gene. Understanding how genetic mutations lead to
retinal degeneration is critical for the development of experimental therapies.

Current research also shows that patients with Stargardt disease could slow its
progression by wearing UV-protective sunglasses and avoiding exposure to bright
light. Researchers have observed that mice which had a mutation of the ABCA4 gene,
and which were reared in dark environments had virtually no lipofuscin deposits.

The disease is often misdiagnosed, or not diagnosed in the first few years of onset,
and this could be the result of little evidence being found during eye examinations.
The discovery of the Stargardt gene could help in a test for the direct diagnosis of the
disease. It is possible that the effect of this newly discovered gene may not be limited
only to juvenile MD, in that it could also aid in the search for causes for age-related
macular degeneration, the leading cause of vision loss in people over age 65.

Currently, there is no effective treatment for Stargardt disease, but having the
genetic "instruction manual" may assist in developing new strategies for therapy.
Also, Advanced Cell Technology announced in November 2010 that the FDA
approved injection of human embryonic stem cells into the eyes of 12 patients
affected by the disease. The study is scheduled to begin in early 2011.

Until treatments are developed, it is important that the learning and working
environment be adapted for people with Stargardt disease. Appropriate low vision aids
and lighting are two important considerations for helping both children and adults to
function as normally as possible.

ERG is normal..