Stargardt disease

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Stargardt disease
Classification and external resources
ICD-10 H35.5
OMIM 248200 600110 603786
DiseasesDB 31282

Stargardt disease, or fundus flavimaculatus, is an inherited form of juvenile macular degeneration that causes progressive vision loss usually to the point of legal blindness. The progression usually starts between the ages of six and twelve years old and plateaus shortly after rapid reduction in visual acuity. Several genes are associated with the disorder. Symptoms typically develop by twenty years of age, and include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.

Signs and symptoms[edit]

The main symptom of Stargardt disease is loss of visual acuity, which ranges from 20/50 to 20/200.[1] Those with Stargardt disease are sensitive to glare; overcast days offer some relief. Vision is most noticeably impaired when the macula (center of retina and focus of vision) is damaged, leaving peripheral vision more intact. Symptoms usually appear before age 20. Symptoms include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.[2][3]

Genetics[edit]

Stargardt disease is associated with several different genes:

  • STGD1: The most common form of Stargardt disease is the recessive form caused by mutations in the ABCA4 gene. It can also be associated with CNGB3.
  • STGD3: There is also a rare dominant form of Stargardt disease caused by mutations in the ELOVL4 gene.
  • STGD4: Associated with PROM1.

The classification "STGD2" is no longer used.

Pathophysiology[edit]

The genetic defect is manifest in the visual phototransduction cycle. The ATP-binding cassette transporter is defective and leads to a build up of a toxic metabolite lipofuscin in the retinal pigmented epithelium.

The form of Stargardt's disease that involves a butterfly pattern of dystrophy is caused by a mutation in a gene that codes a membrane bound protein that is involved in the elongation of very long chain fatty acids (ELOVL4).

Treatment[edit]

No treatments are available for Stargardt's disease.[1] Many patients use magnifiers to help them see, and wear sunglasses to slow the development.[4]

Prognosis[edit]

The long-term prognosis for patients with Stargardt disease is widely variable.[1]

Stargardt disease has no impact on general health and longevity is normal.[5] Some patients are able to drive.

Epidemiology[edit]

Stargardt disease is the most common form of inherited juvenile macular degeneration.[2]

Research[edit]

On November 22, 2010, it was announced that Advanced Cell Technology[6] received United States Food and Drug Administration clearance to immediately initiate a Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy.

In Sept 2011 ACT announced they were beginning the next stage of treatment for SMD, and Dry AMD as the first stage proved to be safe by an independent board of experts.[7] In March 2013, after treating and collecting data on 18 patients, Advanced Cell was given approval to test its stem cell therapy on patients with 20/100 vision.[8]

Recently it was discovered that a new drug can remove lipofuscin from retinal pigment epithelial cells.[9] This opens up a new therapy option for the treatment of Stargardt disease. The drug has now been granted orphan drug designation for the treatment of Stargardt disease by the European Medicines Agency.

History[edit]

The disease was discovered in 1909 by Karl Stargardt, an ophthalmologist in Berlin.[10][11]

In 1997, it was discovered that mutations in the ABCA4 gene cause Stargardt. The mutations cause the production of a dysfunctional protein that cannot perform energy transport to and from photoreceptor cells in the retina. The photoreceptor cells then degenerate, causing vision loss.[2]

References[edit]

  1. ^ a b c Yanoff, Myron; Duker, Jay S. (2008). Ophthalmology (3rd ed.). Edinburgh: Mosby. pp. 560–562. ISBN 978-0323057516. 
  2. ^ a b c Stargardt Disease
  3. ^ "Stargardt's". Lowvision.org. 1997-03-03. Retrieved 2012-12-05. 
  4. ^ Stargardt's Disease: Information for Patients and Their Families
  5. ^ Stargardt Disease from The University of Arizona College of Medicine, Department of Ophthalmology and Vision Science. Retrieved Jan 2012
  6. ^ "Advanced Cell Technology Receives FDA Clearance For the First Clinical Trial Using Embryonic Stem Cells to Treat Macular Degeneration". Advanced Cell Technology. 
  7. ^ "ACT Receives Approval from Data and Safety Monitoring Board (DSMB) to Treat Next Patients in Stem Cell Clinical Trials". Advanced Cell Technology. Retrieved 2012-12-05. 
  8. ^ "Advanced Cell Technology Receives Approval from Data Safety Monitoring Board (DSMB) to Initiate Treatment of Third Patient Cohort in All Three Clinical Trials". Advanced Cell Technology. 2013-03-14. Retrieved 2013-03-17. 
  9. ^ Lipofuscin can be removed from the retinal pigment epithelium of monkeys. Julien S, Schraermeyer U. Neurobiol Aging. 2012 Oct;33(10):2390-7. doi: 10.1016/j.neurobiolaging.2011.12.009. Epub 2012 Jan 12.
  10. ^ synd/2306 at Who Named It?
  11. ^ K. B. Stargardt. Über familiäre, progressive Degeneration in der Makulagegend des Auges. Albrecht von Graefes Archiv für Ophthalmologie, 1909, 71: 534-550.

External links[edit]