Stargardt disease

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Disease Profile

Stargardt disease

1-5 / 10 000

US Estimated

Europe Estimated

Age of onset

Elderly

ICD-10

H35.5

Inheritance

Stargardt disease is most commonly inherited in an autosomal recessive manner.^[1]^[2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

25% (1 in 4) chance to be affected
50% (1 in 2) chance to be an unaffected carrier like each parent
25% chance to be unaffected and not be a carrier

A person with autosomal recessive Stargardt disease will always pass one mutated copy of the gene to each of his/her children. In other words, each of his/her children will at least be a carrier. A child of an affected person can be affected if the other parent is also affected or is a carrier.

In rare cases, Stargardt disease may be inherited in an autosomal dominant manner.^[5] This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause features of the condition. An affected person typically inherits the mutated gene from an affected parent.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Stargardt macular dystrophy; Juvenile onset macular degeneration

Summary

Stargardt disease is a genetic eye disorder that causes progressive vision loss. It affects the macula, an area of the retina responsible for sharp, central vision. Vision loss is due to abnormal accumulation of a fatty yellow pigment (lipofuscin) in the cells within the macula. People with Stargardt disease also have problems with night vision, and some have problems with color vision. The signs and symptoms of Stargardt disease typically appear in late childhood to early adulthood and worsen over time.^[1] It is most commonly caused by mutations in the ABCA4 gene and inherited in an autosomal recessive manner. Rarely it may be caused by mutations in other genes and inherited in an autosomal dominant manner.^[1]^[2] There is currently no treatment, but various services and devices can help affected people carry out daily activities and maintain their independence.^[3]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
100% of people have these symptoms
Reduced visual acuity	Decreased clarity of vision	0007663
80%-99% of people have these symptoms
Abnormal choroid morphology		0000610
Abnormal foveal morphology		0000493
Abnormality of macular pigmentation		0008002
Abnormality of visual evoked potentials		0000649
Central scotoma	Central blind spot	0000603
Color vision defect	Abnormal color vision Abnormality of color vision [ more ]	0000551
Macular degeneration		0000608
Nyctalopia	Night blindness Night-blindness Poor night vision [ more ]	0000662
Paroxysmal involuntary eye movements		0007704
Retinal pigment epithelial atrophy		0007722
Retinal pigment epithelial mottling		0007814
Retinal thinning		0030329
30%-79% of people have these symptoms
Aplasia/Hypoplasia of the macula		0008059
Yellow/white lesions of the macula		0030500
1%-4% of people have these symptoms
Bull's eye maculopathy		0011504
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Retinitis pigmentosa inversa		0008035

Cause

Stargardt disease occurs when the ABCA4 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[4]

Diagnosis

Yes. Genetic testing may help distinguish the type of Stargardt disease a person has, and provide information about the mode of inheritance and risks to other family members. The Genetic Testing Registry (GTR) provides information about the genetic tests available for Stargardt disease. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about genetic testing for this condition should speak with their ophthalmologist or a genetics professional.

Testing Resources

The John and Marcia Carver Nonprofit Genetic Testing Laboratory provides non-profit genetic testing for rare eye diseases to meet a societal need. Click here to read about genetic testing for Stargardt disease.

Treatment

At present there is no cure for Stargardt disease, and there is very little that can be done to slow its progression. Wearing sunglasses to protect the eyes from UVa, UVb and bright light may be of some benefit. Animal studies have shown that taking excessive amounts of vitamin A and beta carotene could promote the additional accumulation of lipofuscin, as well as a toxic vitamin A derivative called A2E; it is typically recommended that these be avoided by individuals with Stargardt disease. There are possible treatments for Stargardt disease that are being tested, including a gene therapy treatment, which has been given orphan drug status by the European Medicines Agency (EMEA, similar to the FDA).^[6] You can read more about this treatment by clicking here. There are also clinical trials involving embryonic stem cell treatments.^[6]

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes multifocal pattern dystrophy simulating STGD1 and retinal and/ or macular dystrophies such as central areolar choroidal dystrophy (CACD), achromatopsia, cone dystrophy (CD) and cone rod dystrophy (CRD). In addition, two autosomal dominant types of macular dystrophy exist that resemble STGD1: STGD3 caused by mutations in the ELOVL4 gene and STGD4 associated with mutations in PROM1. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnosis includes multifocal pattern dystrophy simulating STGD1 and retinal and/ or macular dystrophies such as central areolar choroidal dystrophy (CACD), achromatopsia, cone dystrophy (CD) and cone rod dystrophy (CRD). In addition, two autosomal dominant types of macular dystrophy exist that resemble STGD1: STGD3 caused by mutations in the ELOVL4 gene and STGD4 associated with mutations in PROM1.

Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Macular Degeneration Foundation
PO Box 515
Northampton, MA 01061-0515
Toll-free: 1-888-MACULAR (1-888-622-8527)
Telephone: +1-413-268-7660
E-mail: https://www.macular.org/contact-us
Website: https://www.macular.org/
Foundation Fighting Blindness
7168 Columbia Gateway Drive, Suite 100
Columbia, MD 21046
Toll-free: 1-800-683-5555
Telephone: +1-410-423-0600
TTY: 1-800-683-5551
E-mail: info@fightblindness.org
Website: https://www.fightingblindness.org/
Royal National Institute of Blind People
RNIB Headquarters
105 Judd Street
London
WC1H 9NE
United Kingdom
Telephone: 0303 123 9999
E-mail: helpline@rnib.org.uk
Website: https://www.rnib.org.uk/Pages/Home.aspx

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Foundation Fighting Blindness provides information about Stargardt disease and other retinal diseases.
MedlinePlus Genetics contains information on Stargardt disease. This website is maintained by the National Library of Medicine.
The National Eye Institute (NEI) was established by Congress in 1968 to protect and prolong the vision of the American people. Click on the link to view information on this topic.

In-Depth Information

The American Society of Gene & Cell Therapy provides information on the treatment of genetic eye diseases.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Stargardt disease. Click on the link to view a sample search on this topic.

References

Stargardt macular degeneration. Genetics Home Reference. November 2010; https://ghr.nlm.nih.gov/condition/stargardt-macular-degeneration.
Jane Kelly. STARGARDT DISEASE 1; STGD1. OMIM. June 8, 2015; https://www.omim.org/entry/248200.
Facts About Stargardt Disease. NEI. April, 2015; https://nei.nih.gov/health/stargardt/star_facts.
Tanna P, Strauss RW, Fujinami K, Michaelides M. Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br J Ophthalmol. Jan 2017; 101(1):25-30. https://pubmed.ncbi.nlm.nih.gov/27491360/.
Jane Kelly. STARGARDT DISEASE 3; STGD3. OMIM. September 11, 2006; https://www.omim.org/entry/600110.
Stargardt Disease. American Macular Degeneration Foundation. 2014; https://www.macular.org/stargardt-disease. Accessed 6/4/2014.

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Elderly

H35.5

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.