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Disease Profile
Fabry disease
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000
Age of onset
Childhood
ICD-10
E75.2
Inheritance
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.
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.
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)
Angiokeratoma, diffuse; Anderson-Fabry disease; Hereditary dystopic lipidosis;
Categories
Blood Diseases; Congenital and Genetic Diseases; Eye diseases;
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]
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
|
---|---|---|
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 pulmonary obstruction |
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 |
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
|
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
- 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]
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.
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.
|
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: [email protected]
Website: https://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: [email protected]
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: [email protected]
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: [email protected]
Website: https://www.kidney.org/
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 genetic 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.
References
- Fabry disease. Genetics Home Reference. February 2012; https://ghr.nlm.nih.gov/condition/fabry-disease.
- MehtaA & Hughes DA. Fabry Disease. GeneReviews. 2017; https://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/.
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