Patients With Inherited Retinal Degenerative Diseases Caused By ABCA4 Gene Mutations Should Use Caution When Taking More Than a Daily Recommended Amount of Vitamin A Supplements

After extensive deliberation and discussion of existing and recent new data, members of the FFB's Scientific Advisory Board and outside experts recommend that people with recessive Stargardt disease or cone-rod dystrophy, most of which are caused by mutations in the ABCA4 gene, should avoid intake of vitamin A beyond the recommended daily allowance (RDA). The recommendation comes as a result of research indicating that excess consumption of vitamin A can potentially accelerate vision loss and retinal degeneration in people with recessive Stargardt disease, cone-rod dystrophy, and other retinal conditions caused by variations in the ABCA4 gene. As you will read in the official position paper if you do not know the identity of the gene causing your Stargardt disease or cone-rod dystrophy, please consult with your ophthalmologist and/or genetic counselor about obtaining genetic testing. This recommendation does not have any bearing on typical Retinitis Pigmentosa.

Patients With Inherited Retinal Degenerative Diseases Caused By ABCA4 Gene Mutations Should Use Caution When Taking More Than a Daily Recommended Amount of Vitamin A Supplements

Recommendations:
The Foundation Fighting Blindness recommends that:

  • Based primarily upon a recent animal study, individuals of any age with autosomal recessive Stargardt disease or cone-rod dystrophy caused by ABCA4 gene mutations should be aware of the possible potential risk for further damaging their vision by taking vitamin A supplements (for example, Vitamin A palmitate or other dietary supplements that contain vitamin A) beyond the daily recommended dietary allowance of approximately 3,000 I.U./day for men and 2,333 I.U./day for women, as developed by the Food and Nutrition Board under the aegis of the Institute of Medicine.
  • While there are not definitive data from humans, based on animal studies, individuals with the ABCA4 genetic subtypes of autosomal recessive Stargardt disease or cone-rod dystrophy caused by a mutation in the ABCA4 gene should also consider avoiding excessive sunlight exposure.
  • Individuals who have Stargardt disease or cone-rod dystrophy, but do not know their gene mutation, should consider genetic testing to determine whether they have a mutation in the ABCA4 gene. Information is available from Foundation Fighting Blindness website on how to obtain genetic testing (see below).
  • Before making any changes to diet or lifestyle, individuals with autosomal recessive Stargardt disease or cone rod dystrophy caused by a mutation in the ABCA4 gene, or those individuals who do not know the genetic cause of their retinal degeneration should consult with their personal physician and ophthalmologist regarding these recommendations and possible genetic testing.

Background:
Our understanding of inherited retinal degenerative diseases has dramatically increased with the identification of genes involved in these diseases and with the production of relevant animal models to understand disease progression.

The autosomal recessively transmitted form of Stargardt disease, an early-onset form of macular degeneration, results from mutations in a gene called ABCA4. In individuals with autosomal recessive or isolated forms of Stargardt disease due to mutations in ABCA4, the retinal rod and cone photoreceptor cells of affected individuals cannot efficiently perform their role in a process called the visual cycle. Specifically, the mutant ABCA4 gene does not function in the part of the visual cycle where vitamin A is shuttled back and forth between the photoreceptor cells and a neighboring cell layer called the retinal pigment epithelium (RPE). Consequently, within the RPE, there is the buildup of a toxic vitamin A derivative, called A2E, which collects as yellow-white deposits called lipofuscin.

Some individuals affected by cone-rod dystrophy can also have mutations in the ABCA4 gene and can also exhibit abnormally high lipofuscin accumulation in the RPE.

While direct clinical studies on the use of Vitamin A in individuals with Stargardt disease or cone-rod dystrophy due to mutations in ABCA4 are not available, information from animal studies strongly suggests that taking excessive amounts of vitamin A could promote the additional accumulation of lipofuscin within the RPE cells. Since lipofuscin contains a toxin (A2E), this could lead to a loss of photoreceptor cells and accelerated visual loss. It is currently not entirely certain if this additional accumulation of lipofuscin would lead to a more rapid rate of retinal degeneration in patients with ABCA4 mutations. However, based on the best information that is currently available, we recommend avoiding excess vitamin A intake for those persons. Refraining from excessive use beyond a daily-recommended allowance would be prudent. Again, consult you personal physician before making any changes to your lifestyle or diet.

Based again on animal studies, it is also advisable for patients with ABCA4 gene mutations to consider avoiding excess sunlight exposure to the retina (for example, being outside on a very sunny day without sunglasses), which could potentially accelerate the loss of both RPE and photoreceptor cells. This situation could be helped by using a hat with a large brim and appropriate sunglasses that filter out blue and ultraviolet light, which are potentially the most harmful to the retina.

To determine if this recommendation applies to you, individuals who have Stargardt disease or cone-rod dystrophy who do not already know the genetic reason for their retinal degeneration may want to consider being genetically tested to determine whether they have a mutation in the ABCA4 gene. There are currently CLIA-approved (federally regulated) laboratories that offer a test for ABCA4 mutations in Stargardt disease and cone-rod dystrophy and other laboratories will soon be offering a test for ABCA4 as well. Please visit the Foundation’s website (www.FightBlindness.org) and click the link entitled “Genetic Testing.” This link will take you to the Foundation Fighting Blindness Genetic Testing Information Packet that provides valuable information about genetic testing for retinal degenerative diseases, or call (1-800-683-5555) to obtain a copy of this Packet.

The decision about whether to have a genetic test can be complex and should involve a discussion with an informed clinician and/or a genetic counselor who can advise you about the benefits and limitations of genetic testing and whether other family members should be tested.