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Fabry disease

Classification and external resources

Alpha galactosidase - the protein that is deficient
in Fabry disease.
ICD-10 E75.2 (http://apps.who.int
/2010/en#/E75.2) (ILDS
ICD-9 272.7 (http://www.icd9data.com
OMIM 301500 (http://omim.org/entry
DiseasesDB 4638
MeSH D000795 (http://www.nlm.nih.gov
GeneReviews Fabry disease
Fabry disease
From Wikipedia, the free encyclopedia
Fabry disease (/f!"bri/) (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.
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).
A deficiency of the enzyme alpha
galactosidase A (a-GAL A, encoded by GLA
/data/hgnc_data.php?match=GLA) ) due to
mutation causes a glycolipid known as
globotriaosylceramide (abbreviated as Gb3,
GL-3, or ceramide trihexoside) to accumulate
within the blood vessels, other tissues, and
This accumulation leads to an
impairment of their proper function.
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 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.

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A bilateral, whorl-like corneal
pattern of cream colored lines in a
patient with Fabry disease.
Angiokeratoma, a common
dermatological manifestation in
Fabry sufferers.
The incidence of Fabry disease is estimated to be between 1 in 40,000 to 1 in 120,000 live
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.
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
Fabry disease - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Fabry_disease
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(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.
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,
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,
and was granted marketing approval in the
Fabry disease - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Fabry_disease
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EU in 2001.
FDA approval was applied for the United States.
However, Shire withdrew
their application for approval in the United States in 2012 citing that the agency will require
additional clinical trials before approval.
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), though the latter are usually best avoided in renal disease.
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.
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
Lysosomal storage disorder
Enzyme replacement therapy
^ James, William D.; Berger, Timothy G.; et
al. (2006). Andrews' Diseases of the Skin:
clinical Dermatology. Saunders Elsevier.
p. 538. ISBN 0-7216-2921-0.
^ synd/1761 (http://www.whonamedit.com
/synd.cfm/1761.html) at Who Named It?
^ Karen JK, Hale EK, Ma L (2005).
"Angiokeratoma corporis diffusum (Fabry
disease)" (http://dermatology.cdlib.org
/114/NYU/NYUtexts/0419054.html) .
Dermatol. Online J. 11 (4): 8.
PMID 16403380
/16403380) .

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^ James, William D.; Berger, Timothy G.; et
al. (2006). Andrews' Diseases of the Skin:
clinical Dermatology. Saunders Elsevier.
pp. . ISBN 0-7216-2921-0.
^ Mehta, A.; Ricci, R.; Widmer, U.; Dehout,
F.; Garcia De Lorenzo, A.; Kampmann, C.;
Linhart, A.; Sunder-Plassmann, G.; Ries, M.;
Beck, M. (2004). "Fabry disease defined:
Baseline clinical manifestations of 366
patients in the Fabry Outcome Survey".
European Journal of Clinical Investigation 34
(3): 236242.
/10.1111%2Fj.1365-2362.2004.01309.x) .
PMID 15025684
/15025684) .
^ Hoffmann MD, Bjoern; Beck, Michael PhD;
Sunder-Plassmann, Gere PhD; Borsini,
Walter MD; Ricci, Roberta PhD; Mehta, Atul
MD (JulyAugust 2007). "Nature and
Prevalence of Pain in Fabry Disease and Its
Response to Enzyme Replacement
TherapyA Retrospective Analysis From
the Fabry Outcome Survey.". The Clinical
Journal of Pain 23 (6): 535542.
/10.1097%2FAJP.0b013e318074c986) .

Chew, E; Ghosh, M; McCulloch, C (June
1982). "Amiodarone-induced cornea
verticillata.". Canadian journal of
ophthalmology. Journal canadien
d'ophtalmologie 17 (3): 969. PMID 7116220
/7116220) .
^ Marchesoni CL, Roa N, Pardal AM,
Neumann P, Caceres G, Martinez P,
Kisinovsky I, Bianchi S, Tarabuso AL, Reisin
RC. (2010). "Misdiagnosis in Fabry disease".
J Pediatr. 156 (5): 828831.
/10.1016%2Fj.jpeds.2010.02.012) .
PMID 20385321
/20385321) .
^ Genzyme Drug Shortage Leaves Users
Feeling Betrayed (http://www.nytimes.com
/2010/04/16/business/16genzyme.html) ,
By ANDREW POLLACK, New York Times,
April 15, 2010
^ Keating GM (October 2012). "Agalsidase
alfa: a review of its use in the management
of Fabry disease". BioDrugs 26 (5): 33554.
. PMID 22946754
/22946754) .
^ "Shire Submits Biologics License
Application (BLA) for REPLAGAL with the
U.S. Food and Drug Administration (FDA)"
. FierceBiotech.

Fabry disease - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Fabry_disease
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^ "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.
^ Grogan K (2012-03-15). "Shire withdraws
Replagal in USA as FDA wants more trials"
A_wants_more_trials.aspx) .
^ Waldek, S.; Patel, M. R.; Banikazemi, M.;
Lemay, R.; Lee, P. (2009). "Life expectancy
and cause of death in males and females
with Fabry disease: Findings from the Fabry
Registry". Genetics in Medicine 11 (11):
/10.1097%2FGIM.0b013e3181bb05bb) .
PMID 19745746
/19745746) .
External links
Fabry Disease Information Page (http://www.ninds.nih.gov/disorders/fabrys/fabrys.htm)
Fabry disease (http://ghr.nlm.nih.gov/condition=fabrydisease) at NLM Genetics Home
Fabry Registry (http://www.lsdregistry.net/fabryregistry/)
Stroke in young Fabry patients (http://www.sifap.de)
Support groups
Fabry International Network (http://fabryintnetwork.com/)
Focus on Fabry (http://www.focusonfabry.com/) by Shire
Fabry Community (http://www.fabrycommunity.com) by Genzyme
Fabry Support & Information Group (FSIG) (http://www.fabry.org/)
Fabry support at MPS Society (http://www.mpssociety.co.uk/index.php?page=fabry-
Canadian Fabry Association (http://www.fabrycanada.com)

Fabry disease - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Fabry_disease
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National Fabry Disease Foundation, USA (http://www.fabrydisease.org/)
Fabry Support Group Australia (http://www.fabry.com.au)
Fabry Support Group Poland by Pietka (http://www.fabry.org.pl/jomla/)
Retrieved from "http://en.wikipedia.org/w/index.php?title=Fabry_disease&oldid=612766024"
Categories: X-linked recessive disorders Rare diseases Lipid storage disorders
Skin conditions resulting from errors in metabolism Lysosomal storage diseases
This page was last modified on 13 June 2014 at 13:27.
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