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Fabry's disease


Fabry's disease

Fabry disease
Classification and external resources
10 9 OMIM DiseasesDB eMedicine MeSH D000795

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]


A deficiency of the This accumulation leads to an impairment of their proper function.

The DNA mutations which cause the disease are X-linked dominant 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 that many women suffer with severe symptoms ranging from early cataracts, strokes, to hypertropic 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]


The incidence of Fabry disease is estimated to be between 1 in 40,000 to 1 in 120,000 live births.[5]


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.


Full body or localized pain to the extremities (known as acroparesthesia) or GI tract is common in patients with Fabry disease. Acroparesthesia in Fabry disease 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]

Renal involvement

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.

Cardiac 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. Hypertension (high blood pressure) and cardiomyopathy are commonly observed.

Dermatological manifestations

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 a common symptom.

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

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

Ocular manifestations

Cosmetic 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 fabry patients, and must be differentiated from other causes of vortex keratopathy (e.g. drug deposition in the cornea). This clouding does not affect vision.

Other ocular findings that can be seen include conjunctival aneurysms, posterior spoke-like cataracts, papilloedema, macular edema, optic atrophy and retinal vascular dilation.

Other manifestations

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.


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.[7]


The first treatment for Fabry's disease was approved by FDA on April 24, 2003. Fabrazyme (agalsidase beta) was licensed to the Genzyme Corporation. It is an enzyme replacement therapy (ERT) designed to provide the enzyme that the patient is missing as a result of a genetic malfunction. The drug is expensive — in 2012, Fabrazyme's annual cost was approximately US$200,000 per patient,[8] which is unaffordable to many patients around the world without enough insurance. Enzyme replacement therapy is not a cure, but can allow improved metabolism and partially prevent disease progression, as well as potentially reversing some symptoms.

The pharmaceutical company Shire manufactures agalsidase alpha under the brand name Replagal as a treatment for Fabry's disease,[9] and was granted marketing approval in the EU in 2001.[10] FDA approval was applied for the United States.[11] However, Shire withdrew their application for approval in the United States in 2012 citing that the agency will require additional clinical trials before approval.[12]

Pain associated with Fabry disease can be partially alleviated by ERT, but pain management regimens may also include analgesics, anticonvulsants, and non-steroidal anti-inflammatory drugs (NSAIDs).


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.[13]

Pop Cultural references

  • 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.

See also


External links

  • NIH
  • NLM Genetics Home Reference
  • Fabry Registry
  • Stroke in young Fabry patients
Support groups
  • Fabry International Network
  • Shire
  • 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

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