Fabry disease

Información en español Title

Other Names:

Angiokeratoma, diffuse; Anderson-Fabry disease; Hereditary dystopic lipidosis; Angiokeratoma, diffuse; Anderson-Fabry disease; Hereditary dystopic lipidosis; Alpha-galactosidase A deficiency; GLA deficiency; Angiokeratoma corporis diffusum; Ceramide trihexosidase deficiency See More

Categories:

Blood Diseases; Congenital and Genetic Diseases; Eye diseases; Blood Diseases; Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Kidney and Urinary Diseases; Metabolic disorders; Nervous System Diseases; RDCRN; Skin Diseases See More

Summary Summary

Fabry disease is an inherited disorder that results from the buildup of a particular type of fat in the body's cells, called globotriaosylceramide or GL-3.^[1] Fabry disease affects many parts of the body. Signs and symptoms may include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness of the front part of the eye (corneal opacity); and hearing loss. Potentially severe complications can include progressive kidney damage, heart attack, and stroke. Milder forms of the disorder may appear later in life and affect only the heart or kidneys. Fabry disease is caused by mutations in the GLA gene and is inherited in an X-linked manner.^[2] Treatment may include enzyme replacement therapy (ERT); pain medications, ACE inhibitors; and chronic hemodialysis or renal transplantation for end stage renal disease.^[3]

Last updated: 3/28/2016

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Anemia	Very frequent (present in 80%-99% of cases)
Angiokeratoma	Very frequent (present in 80%-99% of cases)
Arthralgia	Very frequent (present in 80%-99% of cases)
Arthritis	Very frequent (present in 80%-99% of cases)
Congestive heart failure	Very frequent (present in 80%-99% of cases)
Conjunctival telangiectasia	Very frequent (present in 80%-99% of cases)
Corneal dystrophy	Very frequent (present in 80%-99% of cases)
Corneal opacity	Very frequent (present in 80%-99% of cases)
Fatigue	Very frequent (present in 80%-99% of cases)
Hematuria	Very frequent (present in 80%-99% of cases)
Hyperkeratosis	Very frequent (present in 80%-99% of cases)
Hypohidrosis	Very frequent (present in 80%-99% of cases)
Malabsorption	Very frequent (present in 80%-99% of cases)
Myalgia	Very frequent (present in 80%-99% of cases)
Nephrotic syndrome	Very frequent (present in 80%-99% of cases)
Renal insufficiency	Very frequent (present in 80%-99% of cases)
Subcutaneous nodule	Very frequent (present in 80%-99% of cases)
Telangiectasia of the skin	Very frequent (present in 80%-99% of cases)
Transient ischemic attack	Very frequent (present in 80%-99% of cases)
Abnormality of the aortic valve	Frequent (present in 30%-79% of cases)
Abnormality of the renal tubule	Frequent (present in 30%-79% of cases)
Anorexia	Frequent (present in 30%-79% of cases)
Atrioventricular block	Frequent (present in 30%-79% of cases)
Bundle branch block	Frequent (present in 30%-79% of cases)
Cataract	Frequent (present in 30%-79% of cases)
Coarse facial features	Frequent (present in 30%-79% of cases)
Cognitive impairment	Frequent (present in 30%-79% of cases)
Delayed puberty	Frequent (present in 30%-79% of cases)
Emphysema	Frequent (present in 30%-79% of cases)
Hyperlipidemia	Frequent (present in 30%-79% of cases)
Mitral regurgitation	Frequent (present in 30%-79% of cases)
Nausea and vomiting	Frequent (present in 30%-79% of cases)
Nephropathy	Frequent (present in 30%-79% of cases)
Optic atrophy	Frequent (present in 30%-79% of cases)
Proteinuria	Frequent (present in 30%-79% of cases)
Thick lower lip vermilion	Frequent (present in 30%-79% of cases)
Abnormality of femur morphology	Occasional (present in 5%-29% of cases)
Abnormality of the endocardium	Occasional (present in 5%-29% of cases)
Achalasia	Occasional (present in 5%-29% of cases)
Angina pectoris	Occasional (present in 5%-29% of cases)
Anxiety	Occasional (present in 5%-29% of cases)
Chronic obstructive pulmonary disease	Occasional (present in 5%-29% of cases)
Depression	Occasional (present in 5%-29% of cases)
Developmental regression	Occasional (present in 5%-29% of cases)
Diabetes insipidus	Occasional (present in 5%-29% of cases)
Dyspnea	Occasional (present in 5%-29% of cases)
Fever	Occasional (present in 5%-29% of cases)
Glomerulopathy	Occasional (present in 5%-29% of cases)
Hypertension	Occasional (present in 5%-29% of cases)
Hypertrophic cardiomyopathy	Occasional (present in 5%-29% of cases)
Left ventricular hypertrophy	Occasional (present in 5%-29% of cases)
Lymphedema	Occasional (present in 5%-29% of cases)
Reduced bone mineral density	Occasional (present in 5%-29% of cases)
Respiratory insufficiency	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Sensorineural hearing impairment	Occasional (present in 5%-29% of cases)
Vertigo	Occasional (present in 5%-29% of cases)
Abnormality of the hand	-
Arrhythmia	-
Diarrhea	-
Dysautonomia	-
Fasciculations	-
Juvenile onset	-
Left ventricular septal hypertrophy	-
Muscle cramps	-
Myocardial infarction	-
Nausea	-
Obstructive lung disease	-
Paresthesia	-
Tenesmus	-
Vomiting	-
X-linked recessive inheritance	-

Last updated: 9/1/2017

Inheritance Inheritance

Fabry disease is inherited in an X-linked pattern, which means that the gene that causes the condition is located on the X chromosome.^[2]^[3] In males (who have only one X chromosome), one mutated copy of the gene is enough to cause symptoms of the condition. Because females have two copies of the X chromosome, one mutated copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all.^[2]

Last updated: 3/30/2016

Treatment Treatment

Management for Fabry disease may include treatment of specific signs and symptoms as well as prevention of secondary complications.

Treatment for acroparesthesias (pain in the extremities) may include diphenylhydantoin and/or carbamazepine to reduce the frequency and severity of pain crises; or gabapentin, which has also been shown to improve pain.^[4]

Renal insufficiency may be treated with ACE inhibitors. Experts recommend ACE inhibitors for all individuals with evidence of kidney involvement, especially to reduce protein in the urine (proteinuria). Chronic hemodialysis and/or renal transplantation have become lifesaving procedures for affected individuals. The transplanted kidney remains free of the harmful fatty substance (glycosphingolipid) deposition. Therefore, successful renal transplantation corrects the renal function. Transplantation of kidneys from carriers for Fabry disease should be avoided because these kidneys may already be affected. All potential donors that are relatives of the affected individual should be evaluated for their genetic status to make sure they are not affected or a carrier.^[4]

Enzyme replacement therapy (ERT) is generally used to improve some of the the signs and symptoms associated with Fabry disease and to stabilize organ function. Experts have recommended that ERT be started as early as possible in all males with Fabry disease (including children and those with end stage renal disease (ESRD) undergoing dialysis and renal transplantation) and in female carriers that are significantly affected. All of these individuals are at high risk for cardiac, cerebrovascular (interruption of blood supply to the brain), and neurologic complications, such as transient ischemic attacks and strokes. The role of ERT in the long-term prevention of renal, cardiac, and central nervous system (CNS) involvement is unproven; however, because ERT can stabilize organ function in individuals with more advanced disease, some have suggested starting ERT in early disease stages. This might include starting ERT when an individual is asymptomatic.^[4]

Prevention of complications such as renovascular disease (conditions affecting the blood vessels of the kidneys), ischemic heart disease, and cerebrovascular disease in affected individuals is generally the same as for the general population. Measures taken may include ACE inhibitors and/or ARB drugs for proteinuria or albuminemia (high levels of albumin in the blood); blood pressure control; and cholesterol control. Aspirin and other medications may be recommended for the prevention of stroke.^[4]

Surveillance may include yearly or more frequent renal function studies, yearly cardiology evaluation, and yearly hearing evaluation.^[4]

Last updated: 8/2/2011

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Ceramide trihexosidase/alpha-galactosidase A (Brand name: Fabrazyme®) - Manufactured by Genzyme Corporation
FDA-approved indication: For use in patients with Fabry disease to reduce globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types
National Library of Medicine Drug Information Portal

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Fabry disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Patient Registry

The Fabry Registry has been established in order to better understand the natural history of Fabry disease, including disease variations within and between affected families; provide a basis for developing guidelines for disease management; evaluate how treatment affects the course of disease; and provide high-quality data and analysis that will help to continuously develop better treatments.
The Lysosomal Disease Network is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Lysosomal Disease Network has a registry for patients who wish to be contacted about clinical research opportunities.

Organizations 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

Fabry Support & Information Group
108 NE 2nd Street, Ste. C
P.O. Box 510
Concordia, MO 64020-0510
Telephone: 660-463-1355
Fax: 660-463-1356
E-mail: info@fabry.org
Website: http://www.fabry.org
National Fabry Disease Foundation
4301 Connecticut Ave. N.W. Suite 404
Washington, DC 20008-2369
Toll-free: 800-651-9131
Fax: 800-651-9135
E-mail: info@fabrydisease.org
Website: http://www.fabrydisease.org/
National Kidney Foundation
30 East 33rd Street
New York, NY 10016
Toll-free: 800-622-9010
Telephone: 212-889-2210
Fax: 212-689-9261
E-mail: http://www.kidney.org/about/contact.cfm
Website: http://www.kidney.org
National Tay-Sachs and Allied Diseases Association
2001 Beacon Street
Suite 204
Brighton, MA 02135
Toll-free: 800-90-NTSAD (906-8723)
Telephone: 617-277-4463
Fax: 617-277-0134
E-mail: info@ntsad.org
Website: http://www.ntsad.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

You can search here for a Fabry disease physician or staff member on the National Fabry Disease Foundation Web site. Click on the link to go to the search page.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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

The American Society of Gene & Cell Therapy provides information on the treatment of lysosomal storage diseases.
Genetics Home Reference (GHR) contains information on Fabry disease. This website is maintained by the National Library of Medicine.
The National Fabry Disease Foundation offers information and support for Fabry disease. Click on the link to learn more.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Kidney Foundation, Inc. offers an information page on Fabry disease.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
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 Fabry disease. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Ries, et al. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 2006;118:924-932.
Ries, et al. Pediatric Fabry Disease. Pediatrics 2005;115:e344-e355.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Gordon Research Conference and Gordon Research Seminar on Lysosomes and Endocytosis Sunday, June 15, 2014 - Friday, June 20, 2014
Location: Proctor Academy, Andover, NH
Description: The main goal of the Lysosomes and Endocytosis GRC is to foster the dissemination of current research results and the establishment of new research areas and new collaborations in the area of the cell biology of endocytosis, lysosomes, endosomes and related organelles. We hope that many of these new directions and collaborations will be directed toward the etiology, diagnosis and treatment of rare genetic diseases such as lysosomal storage disorders, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Niemann Pick disease and tuberous sclerosis, among others.

Contact: Alexandra Ainsztein, Ph.D.(301) 594-0828, Alexandra.Ainsztein@nih.gov

Co-funding Institute(s): National Institute of General Medical Sciences, Office of Rare Diseases Research
WORLD Symposium 2010 (Lysosomal Disease Network's 6th Annual Research Meeting) Wednesday, February 10, 2010 - Friday, February 12, 2010
Location: Miami Hilton Downtown, Miami, Florida
Description: The specific aims of this meeting were to (1) emphasize the strategies for, and identify the obstacles to, moving from translational research to clinical trials; (2) coalesce members of the LD network into functional research collaborations and present to the LDN community progress on the specific projects that are part of the funded U54 RDCRN grant; (3) foster interdisciplinary collaboration with the overall goal of improving knowledge of basic discoveries and clinical manifestations of these diseases; (4) provide an educational forum for young investigators, clinicians, and researchers in the field; (5) identify and discuss the latest findings in the natural history of lysosomal diseases, diagnostic testing and screening, and treatment, with specific focus on (a) inflammatory components of lysosomal diseases and autophagy, especially in the central nervous system, (b) new treatments of the central nervous systems, and (c) ethics and efficacy in treating the presymptomatic or asymptomatic patient; and (6) identify areas requiring additional basic and clinical research and public policy and regulatory attention, such as ethics and economics, and factors that impact implementation of therapy, including newborn screening.

Contact: Dr. Danilo A. Tagle(301) 496-5745tagled@mninds.nih.gov

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 2715KB)

Related Diseases Related Diseases

The following diseases are related to Fabry disease. If you have a question about any of these diseases, you can contact GARD.

Sphingolipidosis

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

Are there any lifestyle or dietary changes that can have a beneficial effect on the life of Fabry sufferers? See answer
Will Fabry disease affect a transplanted kidney? Previous to the transplant the disease was being managed with an enzyme supplement. Will the enzyme supplement need to be continued? What are, if any, cautions or additional treatments required to manage the disease with a transplanted kidney? See answer
Can women get Fabry disease? See answer

Have a question? Contact a GARD Information Specialist.