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

This disease is grouped under:

Sphingolipidosis

Summary Summary

Fabry disease is a type of lysosomal storage disease. Lysosomes are round structures found in the cells of the body that are full of special proteins called enzymes. Lysosomal enzymes help breakdown other proteins, carbohydrates, fats, and other substances. In Fabry disease, there is not enough of the enzyme alpha-galactosidase (alpha-GAL). Alpha-GAL helps breakdown a fatty acid called "globotriaosylceramide" or GL3 ". Without enough alpha-GAL, the lysosomes become filled with GL-3 and can not work well. ^[1] Symptoms of Fabry disease may include episodes of pain, especially in the hands and feet, 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. Internal organs, such as the kidney, heart or brain, may also be affected, leading to progressive kidney damage, heart attacks, and strokes. Milder forms of Fabry disease may appear later in life and affect only the heart or kidneys. ^[1]^[2]

Fabry disease is caused by certain changes (pathogenic variants, also called mutations) in the GLA gene. Since the GLA gene is located on the X chromosome, Fabry disease is inherited in an X-linked manner.^[1]

Although an enzyme assay test measuring the activity of alpha-GAL can diagnose Fabry disease in males, diagnosis is usually made by genetic testing in both males and females. Treatment may include enzyme replacement therapy (ERT), pain medications, and ACE inhibitors. End stage kidney disease may be treated by dialysis or kidney transplantation.^[2] Migalastat (brand name Galafold) received FDA approval in 2018 to treat some adults who have specific pathogenic variants (mutations) causing Fabry disease. ^[3]

Last updated: 9/5/2018

Symptoms 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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abdominal pain	Pain in stomach Stomach pain [ more ]	0002027
Anemia	Low number of red blood cells or hemoglobin	0001903
Angiokeratoma		0001014
Arthralgia	Joint pain	0002829
Arthritis	Joint inflammation	0001369
Congestive heart failure	Cardiac failure Cardiac failures Heart failure [ more ]	0001635
Conjunctival telangiectasia	Small dilated blood vessels near membrane covering front of eye and eyelids	0000524
Corneal dystrophy		0001131
Corneal opacity		0007957
Fatigue	Tired Tiredness [ more ]	0012378
Hematuria	Blood in urine	0000790
Hyperkeratosis		0000962
Hypohidrosis	Decreased ability to sweat Decreased sweating Sweating, decreased [ more ]	0000966
Malabsorption	Intestinal malabsorption	0002024
Myalgia	Muscle ache Muscle pain [ more ]	0003326
Nephrotic syndrome		0000100
Renal insufficiency	Renal failure Renal failure in adulthood [ more ]	0000083
Subcutaneous nodule	Firm lump under the skin Growth of abnormal tissue under the skin [ more ]	0001482
Telangiectasia of the skin		0100585
Transient ischemic attack	Mini stroke	0002326
30%-79% of people have these symptoms
Abnormal aortic valve morphology		0001646
Abnormal renal tubule morphology		0000091
Anorexia		0002039
Atrioventricular block	Interruption of electrical communication between upper and lower chambers of heart	0001678
Bundle branch block		0011710
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Coarse facial features	Coarse facial appearance	0000280
Cognitive impairment	Abnormality of cognition Cognitive abnormality Cognitive defects Cognitive deficits Intellectual impairment Mental impairment [ more ]	0100543
Delayed puberty	Delayed pubertal development Delayed pubertal growth Pubertal delay [ more ]	0000823
Emphysema		0002097
Hyperlipidemia	Elevated lipids in blood	0003077
Mitral regurgitation		0001653
Nausea and vomiting		0002017
Nephropathy		0000112
Optic atrophy		0000648
Proteinuria	High urine protein levels Protein in urine [ more ]	0000093
Short stature	Decreased body height Small stature [ more ]	0004322
Thick lower lip vermilion	Increased volume of lower lip Plump lower lip Prominent lower lip [ more ]	0000179
5%-29% of people have these symptoms
Abnormal endocardium morphology		0004306
Abnormality of femur morphology	Abnormality of the thighbone	0002823
Achalasia		0002571
Angina pectoris		0001681
Anxiety	Excessive, persistent worry and fear	0000739
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Chronic obstructive pulmonary disease		0006510
Depressivity	Depression	0000716
Developmental regression	Loss of developmental milestones Mental deterioration in childhood [ more ]	0002376
Diabetes insipidus		0000873
Dyspnea	Trouble breathing	0002094
Fever		0001945
Glomerulopathy		0100820
Hypertension		0000822
Hypertrophic cardiomyopathy	Enlarged and thickened heart muscle	0001639
Left ventricular hypertrophy		0001712
Lymphedema	Swelling caused by excess lymph fluid under skin	0001004
Reduced bone mineral density	Low solidness and mass of the bones	0004349
Respiratory insufficiency	Respiratory impairment	0002093
Seizures	Seizure	0001250
Sensorineural hearing impairment		0000407
Vertigo	Dizzy spell	0002321
Percent of people who have these symptoms is not available through HPO
Abnormal autonomic nervous system physiology		0012332
Abnormality of the hand	Abnormal hands Hand anomalies Hand deformities [ more ]	0001155
Diarrhea	Watery stool	0002014
Fasciculations	Muscle twitch	0002380
Juvenile onset	Signs and symptoms begin before 15 years of age	0003621
Lipiduria		0032567
Muscle spasm		0003394
Myocardial infarction	Heart attack	0001658
Nausea		0002018
Obstructive lung disease		0006536
Paresthesia	Pins and needles feeling Tingling [ more ]	0003401
Tenesmus		0012702
Urinary mulberry cells		0032568
Ventricular septal hypertrophy		0005144
Vomiting	Throwing up	0002013
X-linked recessive inheritance		0001419

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 1/1/2020

Do you have updated information on this disease? We want to hear from you.

Inheritance Inheritance

Fabry disease is inherited in an X-linked pattern, which means the genetic changes (pathogenic variants, also called mutations) that cause the disease occur in a gene (the GLA gene) on the X chromosome. Females have two X chromosomes and therefore have two copies of the GLA gene. Males have one X chromosome and one Y chromosome, and therefore have only one copy of the GLA gene.^[1]^[2]

In males, a pathogenic variant in the GLA gene is enough to cause symptoms of Fabry disease, because there is not another working copy of the gene. Females with a pathogenic variant in one copy of the gene can be seemingly asymptomatic, can have severe symptoms, or anything in between. A high percentage of females who have a pathogenic variant experience significant symptoms.^[4]

When a female with a GLA pathogenic variant (with or without symptoms) has children, each child (male or female) has a 50% chance to inherit the GLA pathogenic variant because each child will inherit one of her X chromosomes at random.^[4]

When a male with a GLA pathogenic variant has children, the pathogenic variant will be passed on to all of his daughters, and to none of his sons. Therefore, a male cannot inherit the disease from his father.^[4]

Last updated: 6/24/2019

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.

Treatment Treatment

Management of Fabry disease may include treatment of specific symptoms, as well as medications to prevent or slow the development of secondary complications.^[2]^[3]^[5]^[6]

Phenytoin, carbamazepine,or gabapentin may be used for episodes of severe burning pain in the hands and feet (acroparesthesias).

ACE inhibitors may be used to treat decreased kidney function (renal insufficiency). ACE inhibitors can reduce the loss of protein in the urine (proteinuria). If kidney function continues to decrease dialysis and/or kidney transplantation may be necessary. A kidney transplanted successfully into a person with Fabry disease will remain free of the harmful build up of the fatty acid GL3 and therefore will restore normal kidney function. However it will not stop the buildup of GL3 in other organs or systems of the body. In addition, all potential donors that are relatives of the a person with known Fabry disease should have their genetic status checked to make sure they do not have a pathogenic variant (mutation) in the GLA gene (even if they do not have symptoms).

Enzyme replacement therapy (ERT), human α-Gal A enzyme, may be used to improve symptoms associated with Fabry disease and to stabilize organ function. Studies however suggest ERT may only slightly improve long term outcomes.

Migalastat (Galafold) may also be used to treat certain people with Fabry disease. It works by increasing the activity of the enzyme alpha-GAL, so is different than enzyme replacement therapy (ERT). Migalastat is approved by the United States Food and Drug Administration (FDA) for adults and adolescents 16 years of age and older, with a confirmed diagnosis of Fabry disease and a pathogenic variant (mutation) in the GLA gene that produces an alpha-GAL enzyme that responds to the treatment. About 35 and 50% of the people diagnosed with Fabry may be helped by migalastat. Migalastat has been approved by similar agencies in Europe, Israel, Australia, and Canada, and is registered for approval in other countries.

Medications may be given to control blood pressure and to lower cholesterol levels. Aspirin and similar medications may be recommended to prevent a heart attack.

People with Fabry disease should be seen annually, or more frequently, by a doctor familiar with managing Fabry disease to check the function of their kidneys and heart. Hearing should also be checked annually. Brain imaging is recommended every 2 years. A person with Fabry disease may need a team of specialists in addition to their primary care doctor or pediatrician and genetic specialist, including, depending on symptoms, neurologists, cardiologists (heart doctor), nephrologists (kidney doctor), ophthalmologists (eye doctor), otorhinolaryngologists (ear, nose, and throat doctor), and others.^[2]^[5]

To prevent other complications, medications can be given to control blood pressure and medications to lower cholesterol, and the use of aspirin and similar medications is recommended to prevent heart attack.

Last updated: 9/5/2018

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.

Agalsidase alfa (Brand name: Fabrazyme) - Manufactured by Sanofi Genzyme
FDA-approved indication: April 2003, agalsidase alfa (Fabrazyme) was approved 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
Migalastat hydrochloride (Brand name: Galafold) - Manufactured by Amicus Therapeutics, Inc.
FDA-approved indication: August 2018, migalastat (Galafold) was approved for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.
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.

Related Diseases 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
In childhood, other possible causes of pain such as rheumatoid arthritis and "growing pains" must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Visit the Orphanet disease page for more information.

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 related to 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 supports research for Fabry disease by collecting information about patients with this diagnosis. You can join the registry to share your information with researchers and receive updates about participating in new research studies. Learn more about registries.
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: https://www.fabrydisease.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: https://www.ntsad.org/

Organizations Providing General Support

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: info@kidney.org
Website: https://www.kidney.org/

Do you know of an organization? We want to hear from you.

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

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.
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

FDA Approves New Treatment for Fabry disease
August 22, 2018

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

Have a question? Contact a GARD Information Specialist.

References References

Fabry disease. Genetics Home Reference. February 2012; http://ghr.nlm.nih.gov/condition/fabry-disease.
MehtaA & Hughes DA. Fabry Disease. GeneReviews. 2017; http://www.ncbi.nlm.nih.gov/books/NBK1292/.
FDA approves new treatment for a rare genetic disorder, Fabry disease. FDA U.S. Food and Drug Administration. August 10, 2018; https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616598.htm.
How Is Fabry Disease Inherited?. National Fabry Disease Foundation (NFDF). https://www.fabrydisease.org/index.php/about-fabry-disease/fabry-disease-inheritance. Accessed 6/24/2019.
Desnick R. Genetics of Fabry Disease. MedScape Reference. August 23, 2018; https://emedicine.medscape.com/article/951451-overview.
Benjamin ER, Della Valle MC, Wu X, et al. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genetics in Medicine. 2017; 19(4):430-438. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392595/.