A monogenetic retinal disease caused by a mutation in ABCA4.
ABCA4 is an enzyme that flips a retinoid intermediate of the visual cycle N-retinylidene-phosphatidylethanolamine (N-retPE) from the inner leaflet to the outer leaflet of the photoreceptor outer segment disk membrane.
The most common inherited single-gene retinal disease.
It is usually an autosomal recessive inheritance caused by mutations in the ABCA4 gene.
The carrier frequency in the general population of ABCA4 alleles is 5 to 10%.
Rarely, presents with an autosomal dominant inheritance due to defects with ELOVL4 or PROM1 genes.
Lipofuscin accumulation in the eye, is a major risk factor implicated in macular degeneration, a degenerative disease, and Stargardt disease, an inherited juvenile form of macular degeneration.
It is characterized by macular degeneration.
The genetic defect causes malfunction of the ATP-binding cassette transporter (ABCA4) protein of the visual phototransduction cycle.
Macular degeneration.begins in childhood, adolescence or adulthood, resulting in progressive loss of vision.
Optical coherence tomography is used for diagnosis of Stargardt’s disease.
Presentation usually in childhood or adolescence.
No upper age limit for presentation exists.
The main symptom: loss of visual acuity, uncorrectable with glasses, typically develop before age 20.
Median age of onset of visual symptoms is 17 years.
Visual symptoms include: wavy vision, blind spots, blurriness, loss of depth perception, sensitivity to glare, impaired color vision, and delayed dark adaptation.
A wide variance exists between individuals in the symptoms experienced, and the rate of deterioration in vision.
Peripheral vision is usually better maintained than less fine, central vision.
While it is caused by defects in the ABCA4 gene, other genes such as PROM1 or ELOVL4, or missense mutations may play a play a role.
Severity of Stargardt’s disease is inversely proportional to ABCA4 function .
ABCA4 related disease also has a role to play in other diseases such as retinitis pigmentosa, cone-rod dystrophies and age-related macular degeneration (AMD).
The most common form of Stargardt disease is the recessive form caused by mutations in the ABCA4 gene: STGD1.
Late-onset Stargardt disease is associated with missense mutations of ABCA4.
Defective ABCA4 leads to improper shuttling of vitamin A in the retina, and accelerated formation of toxic vitamin A dimers, known as bisretinoids, and degradation byproducts.
The Vitamin A dimers and other byproducts are widely accepted as the cause of STGD1: damaging the retinal cells, and fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina appear from such damage.
STGD4, encodes a membrane bound protein that is involved in the elongation of very long chain fatty acids (ELOVL4).
Diagnosis is made by history and physical examination usually with a Slit-lamp.
Scanning laser ophthalmoscopy highlights areas of autofluorescence which are associated with retinal pathology.
Spectral-domain optical coherence tomography, electroretinography and microperimetry are also useful for diagnostic and prognostic purposes.
No treatment is available, presently.
Recommendation for harm reduction: reducing retinal exposure to damaging ultra violet light, avoiding foods rich in Vitamin A with the hope of lowering lipofuscin accumulation and maintaining good general health and diet.
Foods, especially carrots, and vitamin supplements rich in vitamin A are considered to be harmful in Stargardt disease.
Often foods with a high vitamin A content are often yellow or orange in color, such as squash, pumpkin, and sweet potato.
Factors that may contribute to more rapid deterioration in Stargardt’s disease are smoking, obesity, and eating unhealthy.
The consumption of oily fish, slows the progression of the disease.
Prognosis is variable and depends on the age of onset and genetic alleles.
The majority of people will progress to legal blindness, but the disease has no impact on general health and life expectancy is normal.
Some patients can maintain a relatively high visual acuity over several years.
A 2017 study reported an incidence of between 1 and 1.28 per 10 000 individuals.
The median age of presentation was 27 years and 90% were symptomatic, with a median visual acuity of Snellen equivalent 20/66.
Gene therapy is designed to insert a copy of a corrected gene into retinal cells.
Stem-cell therapy involves injecting cells with the potential to mature into differentiated and functioning retinal cells.
Retinal implants is being investigated.