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Disease Profile

Fabry disease

Prevalence
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

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Childhood

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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

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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

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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.

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

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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.

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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.

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Not applicable

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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

    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]

    • 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.
    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.
    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.

    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.

    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

      Organizations Providing General Support

        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

          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

              References

              1. Fabry disease. Genetics Home Reference. February 2012; https://ghr.nlm.nih.gov/condition/fabry-disease.
              2. MehtaA & Hughes DA. Fabry Disease. GeneReviews. 2017; https://www.ncbi.nlm.nih.gov/books/NBK1292/.
              3. 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.
              4. 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.
              5. Desnick R. Genetics of Fabry Disease. MedScape Reference. August 23, 2018; https://emedicine.medscape.com/article/951451-overview.
              6. 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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