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Stargardt Macular Degeneration

Stargardt macular degeneration is a disorder belonging to the group of macular dystrophies, genetic disorders of macular degeneration that become clinically apparent during the second and third decade of life. Loss of central vision is the main presentation. The diagnosis requires a detailed physical and ophthalmological examination, an adequate family history, and genetic studies.


Presentation

The clinical presentation of Stargardt macular degeneration (STGD) stems from the accumulation of lipofuscin in the retina and its progressive atrophy, occurring on the grounds of genetic mutations involving substances responsible for retinoid transport away from the outer segments of rods, one of the two types of cells essential for vision [1] [2] [3]. Unlike age-related macular degeneration (AMD), when symptoms are seen after 60 years of age, the onset of progressive central visual loss during the second and third decade of life is the distinguishing feature of SMD [1] [2] [4]. Furthermore, a delay in adaptation to dark (presumably due to atrophy of photoreceptors, in addition to lipofuscin accumulations) is frequently observed [3]. On the basis of patterns of inheritance, STGD can be divided into autosomal recessive (STGD1), which is more common, and autosomal dominant forms (STGD3, or Stargardt-like macular degeneration and STGD4) that can be suspected when a delayed loss of central vision at any point between the second and fifth decades is seen [1] [2] [5]. Gradual loss of visual acuity often leads to blindness, like in other macular dystrophies, but abnormalities of color vision are minimal or absent in STGD, which may be used as an important distinguishing feature [1].

Dentist
  • The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental[newsroom.cumc.columbia.edu]
Long Arm
  • The ELOVL4 gene, located on the long arm of chromosome 6 (6q14), encodes a protein that plays a fatty acid formation of very long chain paper. The ELOVL4 protein is primarily expressed in the retina, but is also expressed in the brain and skin.[ivami.com]
Poor Coordination
  • Poor coordination may be less due to being bad at sports and have more to do with not being able to use their central vision. Another symptom is seeing flecks or spots in their vision.[rebuildyourvision.com]

Workup

Clinical suspicion toward atypical forms of macular degeneration must exist in the presence of a juvenile onset of central vision loss and a delayed adaptation to dark. Firstly, a detailed patient history should determine the exact onset of symptoms. Similar findings in close relatives or siblings may be encountered in all types of STGD, having in mind both autosomal dominant and autosomal recessive patterns of inheritance, thus emphasizing the importance of a detailed family history [1]. After a comprehensive patient interview, a complete ophthalmological exam is necessary. Progressive macular atrophy, with or without the appearance of yellow flecks (composed of lipofuscin) are typically observed on fundoscopy [1]. Moreover, fluorescein angiography is a useful method to distinguish STGD1 from STGD3 by identifying a dark choroid on examination [1]. If valid criteria for STGD exist, genetic studies are necessary to identify specific mutations responsible for the onset of this disorder. Autosomal recessive STGD1 stems from mutations in the photoreceptor cell–specific ATP-binding cassette transporter (ABCR) gene located on chromosome 1p13, whereas genes coding for elongase of very long chain fatty acids-4 (or ELOVL4) located on chromosome 6 are the underlying cause of the autosomal dominant STGD3 and STGD4 [4] [5]. Haplotype analysis is the recommended diagnostic method for detection of mutations in STGD.

Hypercholesterolemia
  • Risk factors include arteriosclerosis, hypercholesterolemia, smoking and hypertension.[giiresearch.com]

Treatment

  • In Phase 3 studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment[visionaware.org]
  • Knowledge of the genetic and molecular basis for ABCA4 related retinal degenerative diseases is being used to develop rationale therapeutic treatments for this set of disorders.[ncbi.nlm.nih.gov]
  • Occasionally, it can be inherited as autosomal dominant. click here for Genetic Inheritance Treatment There is no cure, but research on this and other related diseases may identify a form of treatment See all other forms of Macular Degeneration.[retinaaustraliansw.com.au]
  • The goal of the study, at this phase, is to test the safety and tolerability of the stem cell treatment over a 12 month period, that is, phase I/II will answer the question as to “how safe is the procedure?”[retinaeyedoctor.com]
  • Enrolment in any other clinical treatment study throughout the duration of the SAR422459 study. Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation therapy within the four weeks prior to surgery.[clinicaltrials.gov]

Prognosis

  • “Although we don’t know the prognosis for sure, there is hope. The barrier isn’t science, it’s cost, so we’ve been trying to raise as much money as possible for further research, as well as educating people on the disease.”[express.co.uk]
  • Prognosis - Stargardt Disease Prognosis of Stargardt disease 1: slowly progressing condition Treatment - Stargardt Disease Stargardt disease, like other forms of macular degeneration, does not have a cure yet.[checkorphan.org]
  • Prognosis Due to the high clinical variability, prognosis depends on certain parameters (notably age of onset and electroretinographic findings) that may help the clinician provide the patient with an indication of the course of the disease.[orpha.net]
  • STGD typically has an onset at 10 to 20 years of age, and its earliest symptoms are consistent with slowly progressive central vision loss. 17 Later ages of onset have been associated with a more favorable visual prognosis. 18,19 Cases of asymptomatic[retinatoday.com]

Etiology

  • Etiology STGD1 has been linked to mutations in the ABCA4 gene, which encodes an adenosine triphosphate (ATP)-binding cassette transporter (ABCR) expressed specifically in the cones and rods of the retina.[orpha.net]
  • In the proband with a single ABCA4 mutation and a PRPH2 mutation, the genetic etiology of the disease is less clear.[bmcmedgenet.biomedcentral.com]

Epidemiology

  • Retrieved Jan 2012 The Epidemiology of Stargardt Disease in the United Kingdom Kurt Spiteri Cornish, FRCOphth, Jason Ho, FRCOphth, Susan Downes, FRCOphth, Neil W.[en.wikipedia.org]
  • Summary Epidemiology Worldwide prevalence of STGD1 is estimated at 1/8,000 - 1/10,000. Both sexes are equally affected.[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology Vision loss in Stargardt disease occurs due to the degeneration of the macula. The macula is a small area in the middle of the retina that allows clear, sharp vision when an individual looks straight ahead at an object.[news-medical.net]
  • Late-onset Stargardt disease is associated with missense mutations outside known functional domains of ABCA4. [5] Pathophysiology [ edit ] In STGD1, the genetic defect causes malfunction of the ATP-binding cassette transporter (ABCA4) protein of the visual[en.wikipedia.org]

Prevention

  • NEW YORK – Slowing down the aggregation or “clumping” of vitamin A in the eye may help prevent vision loss caused by macular degeneration, research from Columbia University Medical Center has found.[newsroom.cumc.columbia.edu]
  • Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy. * These authors contributed equally to this work. † To whom correspondence[science.sciencemag.org]
  • Mutations in ABCA4 gene prevents the ABCA4 protein eliminate toxic byproducts of photoreceptor cells. These toxic substances accumulate and form lipofuscin in the photoreceptor cells and surrounding retinal cells, ultimately leading to cell death.[ivami.com]
  • Mutations in the ABCA4 gene prevent the ABCA4 protein from removing toxic byproducts from photoreceptor cells.[ghr.nlm.nih.gov]
  • Researchers continue to look for ways to prevent and treat JMD. Genetic counseling can teach parents about these eye problems and sort out the risks for their children.[webmd.com]

References

Article

  1. Vasireddy V, Wong P, Ayyagaria R. Genetics and molecular pathology of Stargardt-like macular degeneration. Progress in retinal and eye research. 2010;29(3):191-207.
  2. Hubbard AF, Askew EW, Singh N, Leppert M, Bernstein PS. Association of adipose and red blood cell lipids with severity of dominant Stargardt macular dystrophy (STGD3) secondary to an ELOVL4 mutation. Arch Ophthalmol. 2006;124(2):257-263.
  3. Maugeri A, Meire F, Hoyng CB, et al. A novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like macular dystrophy. Invest Ophthalmol Vis Sci. 2004;45(12):4263-4267.
  4. Briggs CE, Rucinski D, Rosenfeld PJ, Hirose T, Berson EL, Dryja TP. Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration. Invest Ophthalmol Vis Sci. 2001;42(10):2229-2236.
  5. McMahon A, Jackson SN, Woods AS, Kedzierski W. A Stargardt disease-3 mutation in the mouse Elovl4 gene causes retinal deficiency of C32-C36 acyl phosphatidylcholines. FEBS lett. 2007;581(28):5459-5463.

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Last updated: 2019-07-11 20:11