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Fabry disease

Reviewed March 2007

What is Fabry disease?

Fabry disease is an inherited disorder that results from the buildup of a particular type of fat in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease 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. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Milder forms of the disorder may appear later in life and affect only the heart or kidneys.

How common is Fabry disease?

Fabry disease affects an estimated 1 in 40,000 to 60,000 males. This disorder also occurs in females, although less frequently. Milder, late-onset forms of the disorder are probably more common than the classic, severe form.

What genes are related to Fabry disease?

Mutations in the GLA gene cause Fabry disease.

The GLA gene provides instructions for making an enzyme called alpha-galactosidase A. This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. Alpha-galactosidase A normally breaks down a fatty substance called globotriaosylceramide. Mutations in the GLA gene alter the structure and function of the enzyme, preventing it from breaking down this substance effectively. As a result, globotriaosylceramide builds up in cells throughout the body, particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. The progressive accumulation of this substance damages cells, leading to the varied signs and symptoms of Fabry disease.

GLA mutations that result in an absence of alpha-galactosidase A activity lead to the classic, severe form of Fabry disease. Mutations that decrease but do not eliminate the enzyme's activity usually cause the milder, late-onset forms of Fabry disease that affect only the heart or kidneys.

How do people inherit Fabry disease?

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered 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.

Unlike other X-linked disorders, Fabry disease causes significant medical problems in many females who have one altered copy of the GLA gene. These women may experience many of the classic features of the disorder, including nervous system abnormalities, kidney problems, chronic pain, and fatigue. They also have an increased risk of developing high blood pressure, heart disease, stroke, and kidney failure. The signs and symptoms of Fabry disease usually begin later in life and are milder in females than in their affected male relatives.

Some females who carry a mutation in one copy of the GLA gene never have any of the signs and symptoms of Fabry disease.

Where can I find information about treatment for Fabry disease?

You may find information on treatment or management of Fabry disease or some of its symptoms in the links below, particularly the links for Gene Reviews, Educational resources, and Patient support.

Where can I find additional information about Fabry disease?

You may find the following resources about Fabry disease helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Health Topic: Genetic Brain Disorders (http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html)
    • Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/GARD/Disease.aspx?PageID=4&DiseaseID=6400)
  • Additional NIH Resources - National Institutes of Health
    • National Institute of Neurological Disorders and Stroke: Fabry's Disease Information Page (http://www.ninds.nih.gov/disorders/fabrys/fabrys.htm)
    • National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet (http://www.ninds.nih.gov/disorders/lipid_storage_diseases/detail_lipid_storage_diseases.htm)
  • Educational resources - Information pages
    • Ask the Geneticist: Diagnosis of Fabry disease (http://www.askthegen.org/question.php?question_id=1641)
    • Ask the Geneticist: Enzyme replacement therapy for Fabry disease (http://www.askthegen.org/question.php?question_id=1241)
    • Emory University School of Medicine (http://www.genetics.emory.edu/pdf/Fabry.PDF)
    • International Center for Fabry Disease, Mount Sinai School of Medicine (http://www.mssm.edu/genetics/fabry/)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,442/)
    • Merck Manual of Medical Information, Second Home Edition (http://www.merck.com/mmhe/sec23/ch282/ch282d.html#sec23-ch282-ch282d-1480)
    • National Kidney Foundation (http://www.kidney.org/atoz/atozItem.cfm?id=61)
    • New York Online Access to Health (http://www.noah-health.org/en/bns/disorders/other/fabry.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=324)
    • The Cleveland Clinic Health Information Center (http://my.clevelandclinic.org/disorders/Fabrys_Disease/hic_Fabrys_Disease.aspx)
    • UpToDate Patient Information (http://patients.uptodate.com/topic.asp?file=renldis/22850&title=Fabry+disease)
  • Patient support - For patients and families
    • Children Living With Inherited Metabolic Diseases (CLIMB) (UK) (http://www.climb.org.uk/)
    • Fabry Support & Information Group (http://www.Fabry.org)
    • Genetic Alliance (http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Fabry+Disease&expand=Treatment)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Fabry+Disease)
    • National Tay-Sachs & Allied Diseases Association, Inc. (http://www.ntsad.org/)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/metaboli.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fabry)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=2775)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22Fabry+disease%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Fabry+Disease[MAJR])+AND+(Fabry+disease[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=720+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): α-Galactosidase A Deficiency: Fabry Disease (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=150)

What other names do people use for Fabry disease?

  • Alpha-galactosidase A deficiency
  • Anderson-Fabry Disease
  • Angiokeratoma Corporis Diffusum
  • Angiokeratoma diffuse
  • Ceramide trihexosidase deficiency
  • Fabry's Disease
  • GLA deficiency
  • Hereditary dystopic lipidosis

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Fabry disease?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding Fabry disease?

angiokeratoma ; cardiac ; cell ; ceramides ; chromosome ; chronic ; complication ; deficiency ; enzyme ; gene ; heart attack ; hypohidrosis ; kidney ; lysosome ; mutation ; nervous system ; renal ; sex chromosomes ; sign ; symptom

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Deegan PB, Baehner AF, Barba Romero MA, Hughes DA, Kampmann C, Beck M; European FOS Investigators. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet. 2006 Apr;43(4):347-52. Epub 2005 Oct 14. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16227523)
  • Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med. 2003 Feb 18;138(4):338-46. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12585833)
  • Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, Bultas J, Lee P, Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006 Sep;8(9):539-48. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16980809)
  • Feldt-Rasmussen U, Rasmussen AK, Mersebach H, Rosenberg KM, Hasholt L, Sorensen SA. Fabry disease--a metabolic disorder with a challenge for endocrinologists? Horm Res. 2002;58(6):259-65. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12446988)
  • Gene Review (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fabry)
  • Hauser AC, Lorenz M, Sunder-Plassmann G. The expanding clinical spectrum of Anderson-Fabry disease: a challenge to diagnosis in the novel era of enzyme replacement therapy. J Intern Med. 2004 Jun;255(6):629-36. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15147526)
  • Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H, Ponzone A, Desnick RJ. High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet. 2006 Jul;79(1):31-40. Epub 2006 Apr 28. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16773563)
  • Wang RY, Lelis A, Mirocha J, Wilcox WR. Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007 Jan;9(1):34-45. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17224688)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2007
Published: May 4, 2009