Fabry's disease: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 20: Line 20:
==Overview==
==Overview==
'''Fabry disease''' is an [[X-linked recessive]] inherited [[lysosomal storage disease]], characterized by abnormal accumulation of ceramide trihexose in cardiovascular and renal systems.
'''Fabry disease''' is an [[X-linked recessive]] inherited [[lysosomal storage disease]], characterized by abnormal accumulation of ceramide trihexose in cardiovascular and renal systems.
==Historical Perspective==
It is named for Johannes Fabry.<ref>{{WhoNamedIt|synd|1761}}</ref>
==Classification==
*Non-neuropathic form
*Neuropathic form
**Infantile form
**Juvenile form


==Pathophysiology==
==Pathophysiology==
A deficiency of the [[enzyme]] [[alpha galactosidase|alpha galactosidase A]] causes a [[glycolipid]] known as globotriaosylceramide (also abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the [[blood vessel]]s, other tissues, and organs. This accumulation leads to an impairment of their proper function. The condition affects [[Zygosity|hemizygous]] males, as well as both [[Zygosity|heterozygous]] and [[Zygosity|homozygous]] females; males tend to experience the most severe clinical symptoms, while females vary from virtually no symptoms to those as serious as males. This variability is thought to be due to [[X-inactivation]] patterns during embryonic development of the female.
*Fabry's disease follows an X-linked recessive inheritance pattern.
*A deficiency of the [[enzyme]] [[alpha galactosidase|alpha galactosidase A]] causes a [[glycolipid]] known as globotriaosylceramide (also abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the [[blood vessel]]s, mononuclear phagocytes, neurons, other tissues, and organs.
*This accumulation leads to an impairment of their proper function. The condition affects [[Zygosity|hemizygous]] males, as well as both [[Zygosity|heterozygous]] and [[Zygosity|homozygous]] females; males tend to experience the most severe clinical symptoms, while females vary from virtually no symptoms to those as serious as males.
*This variability is thought to be due to [[X-inactivation]] patterns during embryonic development of the female.


==Symptoms==
==Epidemiology and Demographics==
Symptoms include [[anhidrosis]], [[fatigue (medical)|fatigue]], and red spots on skin. Some of the most common pathological symptoms includes skin [[lesions]] ([[angiokeratoma]]s), and a burning pain of the extremities. This pain can become very intense, especially when one has a fever. Angiokeratomas are tiny, painless [[papules]] that appear at any region of the body, but are predominant on the thighs, buttocks, lower abdomen, and groin. Ocular involvement may be present showing cornea verticillata (also known as vortex keratopathy); this corneal whorling does not have any effect on vision or eye function. 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 or ignorance. Manifestations of the disease usually increase in number and severity as an individual ages.
The prevalence of Fabry disease is estimated to range from 1:17,000 to 1:117,000 males in Caucasian populations.<ref name="pmid11889412">{{cite journal |author=Branton MH, Schiffmann R, Sabnis SG, ''et al.'' |title=Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course |journal=[[Medicine]] |volume=81 |issue=2 |pages=122–38 |year=2002 |month=March |pmid=11889412 |doi= |url=}}</ref><ref name="pmid9918480">{{cite journal |author=Meikle PJ, Hopwood JJ, Clague AE, Carey WF |title=Prevalence of lysosomal storage disorders |journal=[[JAMA : the Journal of the American Medical Association]] |volume=281 |issue=3 |pages=249–54 |year=1999 |month=January |pmid=9918480 |doi= |url=}}</ref>
 
==Diagnosis==
===Symptoms===
*Lack of sweating ([[anhidrosis]]) or decreased sweating
*[[fatigue (medical)|Fatigue]]
*Red spots on skin ([[angiokeratoma]]s): tiny, painless [[papules]] that appear at any region of the body, but are predominant on the thighs, buttocks, lower abdomen, and groin.
*Burning pain of the extremities. This pain can become very intense, especially when one has a fever.
*[[Loss of vision]] or blurry vision from corneal opacities.
*[[Abdominal pain]]
*[[Chest pain]] and [[palpitations]]
*[[Delayed puberty]]
*[[Pyrexia of unknown origin]]
*[[cyanosis]] of extremities on exposure to cold ([[Raynaud's phenomenon]])
*[[Hearing loss]]
*[[Loss of sensations]] in extremities
*[[Telangiectasis]]
 
===Physical Examination===


Kidney complications are a common and serious effect of the disease; [[renal insufficiency]] and [[renal failure]] may worsen throughout life. [[Proteinuria]] is often the first sign of kidney involvement. [[Cardiac]] complications occur when Gb3 builds up in different heart cells; heart related effects worsen with age and may lead to increased risk of heart disease. Cerebrovascular effects lead to an increased risk of stroke. Other symptoms include an inability or decreased ability to sweat, fatigue, ringing in the ears ([[tinnitus]]), [[Vertigo (medical)|vertigo]], nausea, and diarrhea.


Fabry's disease may also have ocular involvement, such as the presence of corneal verticillata in the basal layers of the epithelium, conjunctival aneursyms, and spokelike cataracts.  Papilledema, macular edema, optic atrophy and retinal vascular dilation may also be present.


==Treatment==
==Treatment==
Until recently, treatment of Fabry disease targeted the [[symptomatic]] effects.  However, it is currently being treated at the cellular level through enzyme replacement therapy using [[Agalsidase alpha]] (Replagal) and [[Agalsidase beta]] (Fabrazyme®).  The cost of these drugs is problematic (approximately $170,000 US a year/patient) and remains a barrier to many patients in some countries. Enzyme replacement therapy (typically infused every two weeks) may be performed in the patient's home by the patients themselves. Enzyme replacement therapy is not a cure, and must be infused recurrently for maximum benefit.
Until recently, treatment of Fabry disease targeted the [[symptomatic]] effects.  However, it is currently being treated at the cellular level through enzyme replacement therapy using [[Agalsidase alpha]] (Replagal) and [[Agalsidase beta]] (Fabrazyme®).  The cost of these drugs is problematic (approximately $170,000 US a year/patient) and remains a barrier to many patients in some countries. Enzyme replacement therapy (typically infused every two weeks) may be performed in the patient's home by the patients themselves. Enzyme replacement therapy is not a cure, and must be infused recurrently for maximum benefit.
==Eponym==
* It is named for Johannes Fabry.<ref>{{WhoNamedIt|synd|1761}}</ref>


==References==
==References==

Revision as of 20:29, 13 August 2012

Template:DiseaseDisorder infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Synonyms and keywords: Anderson-Fabry disease; angiokeratoma corporis diffusum universale; alpha-glucosidase A deficiency; ceramide trihexosidase deficiency; hereditary dystopic lipidosis; GLA deficiency; Sweeley-Klionsky disease

Overview

Fabry disease is an X-linked recessive inherited lysosomal storage disease, characterized by abnormal accumulation of ceramide trihexose in cardiovascular and renal systems.

Historical Perspective

It is named for Johannes Fabry.[1]

Classification

  • Non-neuropathic form
  • Neuropathic form
    • Infantile form
    • Juvenile form

Pathophysiology

  • Fabry's disease follows an X-linked recessive inheritance pattern.
  • A deficiency of the enzyme alpha galactosidase A causes a glycolipid known as globotriaosylceramide (also abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the blood vessels, mononuclear phagocytes, neurons, other tissues, and organs.
  • This accumulation leads to an impairment of their proper function. The condition affects hemizygous males, as well as both heterozygous and homozygous females; males tend to experience the most severe clinical symptoms, while females vary from virtually no symptoms to those as serious as males.
  • This variability is thought to be due to X-inactivation patterns during embryonic development of the female.

Epidemiology and Demographics

The prevalence of Fabry disease is estimated to range from 1:17,000 to 1:117,000 males in Caucasian populations.[2][3]

Diagnosis

Symptoms

Physical Examination

Treatment

Until recently, treatment of Fabry disease targeted the symptomatic effects. However, it is currently being treated at the cellular level through enzyme replacement therapy using Agalsidase alpha (Replagal) and Agalsidase beta (Fabrazyme®). The cost of these drugs is problematic (approximately $170,000 US a year/patient) and remains a barrier to many patients in some countries. Enzyme replacement therapy (typically infused every two weeks) may be performed in the patient's home by the patients themselves. Enzyme replacement therapy is not a cure, and must be infused recurrently for maximum benefit.

References

  1. ↑ Template:WhoNamedIt
  2. ↑ Branton MH, Schiffmann R, Sabnis SG; et al. (2002). "Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course". Medicine. 81 (2): 122–38. PMID 11889412. Unknown parameter |month= ignored (help)
  3. ↑ Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999). "Prevalence of lysosomal storage disorders". JAMA : the Journal of the American Medical Association. 281 (3): 249–54. PMID 9918480. Unknown parameter |month= ignored (help)

External links


de:Morbus Fabry fi:Fabryn tauti

Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Fabry%27s_disease&oldid=683095"