Some science behind the scenes

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.

The incidence of Fabry disease is estimated to be between one in 40,000 and one in 120,000 live births.  The disease is named after one of its discoverers, Johannes Fabry (June 1, 1860 – June 29, 1930).

Symptoms

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.

  • Pain - 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.
  • Kidney involvement - Kidney complications are a common and serious effect of the disease; kidney insufficiency and kidney failure may worsen throughout life. The presence of protein in the urine (which causes foamy urine) is often the first sign of kidney involvement. End-stage kidney failure in those with Fabry disease typically occurs in the third decade of life.
  • 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.
  • 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 common.
  • Anhidrosis (lack of sweating) is a common symptom, and less commonly hyperhidrosis (excessive sweating).
  • Ocular involvement  - may be present showing cornea verticillata (also known as vortex keratopathy), i.e. clouding of the corneas. Other ocular findings can include conjunctival and retinal vascular abnormalities, and anterior/posterior spoke-like cataract. Visual reduction from these manifestations are uncommon.
  • 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.[citation needed]

Cause

A deficiency of the enzyme alpha galactosidase A (a-GAL A, encoded by GLA) due to mutation.

This causes a glycolipid known as globotriaosylceramide (abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the blood vessels, other tissues, and organs. This accumulation leads to an impairment of their proper functions.  The DNA mutations which cause the disease are X-linked recessive.

Although the cause of the various manifestations is a mutation in the gene, this is not in fact the actual cause, as we need to know what caused the mutation.

As the problem here is a generic one for all inherited diseases caused by mutation it is discussed in the section Inherited illness, please follow the link.

References

  • 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". The Clinical Journal of Pain 23 (6): 535–542. doi:10.1097/AJP.0b013e318074c986. PMID 17575495.
  • Karen, Julie K.; Hale, Elizabeth K.; Ma, Linglei (2005). "Angiokeratoma corporis diffusum (Fabry disease)". Dermatology Online Journal 11 (4): 8. PMID 16403380.
  • 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". The Journal of Pediatrics 156 (5): 828–31. doi:10.1016/j.jpeds.2010.02.012. PMID 20385321.
  • 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". Genetics in Medicine 11 (11): 790–796. doi:10.1097/GIM.0b013e3181bb05bb. PMID 19745746.
  • 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. doi:10.1111/j.1365-2362.2004.01309.x. PMID 15025684.

Observations

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