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Fabry disease

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Title: Fabry disease  
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Subject: List of genetic disorders, List of MeSH codes (C18), Lipid storage disorder, List of MeSH codes (C16), Lysosomal storage disease
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Fabry disease

Fabry disease
Alpha galactosidase - the deficient protein Fabry disease
Classification and external resources
ICD-10 E75.2 (ILDS E75.25)
ICD-9-CM 272.7
OMIM 301500
DiseasesDB 4638
eMedicine neuro/579 derm/707 ped/2888
MeSH D000795
  • Fabry disease

Fabry disease () (also known as Fabry's disease, Anderson-Fabry disease, angiokeratoma corporis diffusum, and alpha-galactosidase A deficiency) is a rare genetic lysosomal storage disease, inherited in an X-linked manner. Fabry disease can cause a wide range of systemic symptoms.[1] It is a form of sphingolipidosis, as it involves dysfunctional metabolism of sphingolipids. The disease is named after one of its discoverers, Johannes Fabry (June 1, 1860 – June 29, 1930).[2]


  • Pathophysiology 1
  • Incidence 2
  • Symptoms 3
    • Pain 3.1
    • Renal involvement 3.2
    • Cardiac manifestations 3.3
    • Dermatological manifestations 3.4
    • Other manifestations 3.5
  • Diagnosis 4
  • Treatment 5
  • Prognosis 6
  • Pop culture references 7
  • See also 8
  • References 9
    • Sources and Further reading 9.1
  • External links 10


A deficiency of the

  • Focus on Fabry by Shire
  • Fabry Community by Genzyme
  • Fabry Support & Information Group (FSIG)
  • Fabry support at MPS Society
  • Canadian Fabry Association
  • National Fabry Disease Foundation, USA
  • Fabry Support Group Australia
  • Fabry Support Group Poland by Pietka
Support groups
  • Fabry Disease Information Page at NINDS
  • Fabry disease at NLM Genetics Home Reference
  • Fabry Registry
  • Stroke in young Fabry patients
  • Datagenno - Fabry Disease

External links

  • James, William D.; Berger, Timothy G.; Elston, Dirk (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier.  
  • Schiffmann, Raphael; Kopp, Jeffrey B.; Austin, Howard A.; Sabnis, Sharda; Moore, David F.; Weibel, Thais; Balow, James E.; Brady, Roscoe O. (June 2001). "Enzyme replacement therapy in Fabry disease: a randomized controlled trial".  
  • Wilcox, William R.; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E.; Desnick, Robert J.; Germain, Dominique P. (July 2004). "Long-term safety and efficacy of enzyme replacement therapy for Fabry disease".  

Sources and Further reading

  1. ^ James, Berger & Elston 2006, p. 538
  2. ^ synd/1761 at Who Named It?
  3. ^ Karen, Julie K.; Hale, Elizabeth K.; Ma, Linglei (2005). "Angiokeratoma corporis diffusum (Fabry disease)".  
  4. ^ James, Berger & Elston 2006, pp. 
  5. ^ Mehta, A.; Ricci, R.; Widmer, U.; Dehout, F.; Garcia de Lorenzo, A.; Kampmann, C.; Linhart, A.; Sunder-Plassmann, G.; Ries, M.; Beck, M. (March 2004). "Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey". European Journal of Clinical Investigation 34 (3): 236–42.  
  6. ^ Hoffmann, Bjoern; Beck, Michael; Sunder-Plassmann, Gere; Borsini, Walter; Ricci, Roberta; Mehta, Atul (2007). "Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapy—a retrospective analysis from the Fabry Outcome Survey".  
  7. ^ a b Chew, E.; Ghosh, M.; McCulloch, C. (June 1982). "Amiodarone-induced cornea verticillata". Canadian Journal of Ophthalmology 17 (3): 96–99.  
  8. ^ Marchesoni, Cintia L.; Roa, Norma; Pardal, Ana María; Neumann, Pablo; Cáceres, Guillermo; Martínez, Pablo; Kisinovsky, Isaac; Bianchi, Silvia; Tarabuso, Ana Lía; Reisin, Ricardo C. (May 2010). "Misdiagnosis in Fabry disease".  
  9. ^ "Fabrazyme Prescribing Information (USA)" (PDF). 
  10. ^ Pollack, Andrew (April 15, 2010). "Genzyme Drug Shortage Leaves Users Feeling Betrayed".  
  11. ^ Fervenza, Fernando C.; Torra, Roser; Warnock, David G. (December 2008) [13 November 2008]. "Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease".  
  12. ^ Keating, Gillian M. (October 2012). "Agalsidase alfa: a review of its use in the management of Fabry disease".  
  13. ^ "Shire Submits Biologics License Application (BLA) for Replagal with the U.S. Food and Drug Administration (FDA)". FierceBiotech. 
  14. ^ "With A Life-Saving Medicine In Short Supply, Patients Want Patent Broken". 2010-08-04. Archived from the original on 14 September 2010. Retrieved 2010-09-02. 
  15. ^ Grogan, K. (2012-03-15). "Shire withdraws Replagal in USA as FDA wants more trials". PharmaTimes. 
  16. ^ Waldek, Stephen; Patel, Manesh R.; Banikazemi, Maryam; Lemay, Roberta; Lee, Philip (November 2009). "Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry".  


See also

  • House ("Epic Fail", season 6 episode 3) centers on a patient with Fabry disease.
  • Scrubs ("My Catalyst", season 3 episode 12) features a Fabry disease diagnosis.
  • Crossing Jordan ("There's No Place Like Home", season 2 episode 1) features a patient who died suffering Fabry disease.

Pop culture references

Life expectancy with Fabry disease for males was 58.2 years, compared with 74.7 years in the general population, and for females 75.4 years compared with 80.0 years in the general population, according to registry data from 2001 to 2008. The most common cause of death was cardiovascular disease, and most of those had received kidney replacements.[16]


Pain associated with Fabry disease may be partially alleviated by ERT in some patients, but pain management regimens may also include analgesics, anticonvulsants, and nonsteroidal anti-inflammatory drugs, though the latter are usually best avoided in renal disease.

The pharmaceutical company Shire manufactures agalsidase alpha (which differs in the structure of its oligosaccharide side chains[11]) under the brand name Replagal as a treatment for Fabry's disease,[12] and was granted marketing approval in the EU in 2001.[13] FDA approval was applied for the United States.[14] However, Shire withdrew their application for approval in the United States in 2012, citing that the agency will require additional clinical trials before approval.[15]

The first treatment for Fabry's disease was approved by the US FDA on April 24, 2003. Fabrazyme (agalsidase beta, or Alpha-galactosidase) was licensed to the Genzyme Corporation.[9] It is an enzyme replacement therapy (ERT) designed to provide the enzyme the patient is missing as a result of a genetic malfunction. The drug is expensive — in 2012, Fabrazyme's annual cost was about US$200,000 per patient,[10] which is unaffordable to many patients around the world without enough insurance. ERT is not a cure, but can allow improved metabolism and partially prevent disease progression, as well as potentially reverse some symptoms.


Fabry disease is suspected based on the individual's clinical presentation, and can be diagnosed by an enzyme assay (usually done on leukocytes) to measure the level of alpha-galactosidase activity. An enzyme assay is not reliable for the diagnosis of disease in females due to the random nature of X-inactivation. Molecular genetic analysis of the GLA gene is the most accurate method of diagnosis in females, particularly if the mutations have already been identified in male family members. Many disease-causing mutations have been noted. Kidney biopsy may also be suggestive of Fabry disease if excessive lipid buildup is noted. Pediatricians, as well as internists, commonly misdiagnose Fabry disease.[8]


Fatigue, neuropathy (in particular, burning extremity pain), cerebrovascular effects leading to an increased risk of stroke, tinnitus (ringing in the ears), vertigo, nausea, inability to gain weight, chemical imbalances, and diarrhea are other common symptoms.

Other manifestations

Other ocular findings can include conjunctival and retinal vascular abnormalities, and anterior/posterior spoke-like cataract. Visual reduction from these manifestastions are uncommon.

Ocular involvement may be present showing cornea verticillata (also known as vortex keratopathy), i.e. clouding of the corneas. Keratopathy may be the presenting feature in asymptomatic patients, and must be differentiated from other causes of vortex keratopathy (e.g. drug deposition in the cornea).[7] This clouding does not affect vision.[7]

Additionally, patients can exhibit Raynaud's disease-like symptoms with neuropathy (in particular, burning extremity pain).

Anhidrosis (lack of sweating) is a common symptom, and less commonly hyperhidrosis (excessive sweating).

Angiokeratomas (tiny, painless papules that can appear on any region of the body, but are predominant on the thighs, around the belly button, buttocks, lower abdomen, and groin) are common.

Dermatological manifestations

Cardiac complications occur when glycolipids build up in different heart cells; heart-related effects worsen with age and may lead to increased risk of heart disease. High blood pressure and cardiomyopathy are commonly observed.

Cardiac manifestations

Kidney complications are a common and serious effect of the disease; renal insufficiency and renal failure may worsen throughout life. Proteinuria (which causes foamy urine) is often the first sign of kidney involvement. End-stage renal failure in Fabry patients can typically occur in the third decade of life, and is a common cause of death due to the disease.

Renal involvement

Full body or localized pain to the extremities (known as acroparesthesia) or gastrointestinal (GI) tract is common in patients with Fabry disease. This acroparesthesia is believed to be related to the damage of peripheral nerve fibers that transmit pain. GI tract pain is likely caused by accumulation of lipids in the small vasculature of the GI tract which obstructs blood flow and causes pain.[6]


Symptoms are typically first experienced in early childhood and can be very difficult to understand; the rarity of Fabry disease to many clinicians sometimes leads to misdiagnoses. Manifestations of the disease usually increase in number and severity as an individual ages.

Angiokeratoma, a common dermatological manifestation in Fabry sufferers
A bilateral, whorl-like corneal pattern of cream -colored lines in a patient with Fabry disease


The incidence of Fabry disease is estimated to be between one in 40,000 and one in 120,000 live births.[5]


The DNA mutations which cause the disease are X-linked recessive with incomplete penetrance in heterozygous females. The condition affects hemizygous males (i.e. all males), as well as homozygous, and in many cases heterozygous females. While males typically experience severe symptoms, women can range from being asymptomatic to having severe symptoms. New research suggests many women suffer with severe symptoms ranging from early cataracts or strokes to hypertrophic left ventricular heart problems and renal failure. This variability is thought to be due to X-inactivation patterns during embryonic development of the female.[4]

This accumulation leads to an impairment of their proper functions. [3]

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