Fabry disease runs in families. It can have lots of different symptoms, including pain in the hands and feet and a specific kind of rash.When you have Fabry disease, a certain type of fatty substance builds up in your body. It narrows your blood vessels, which can hurt your skin, kidneys, heart, brain, and nervous system.

1. By
Farshid mokhberi
Shahid beheshti University of Medical Sciences

3. Definition:
 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. It is a form of sphingolipidosis, as
it involves dysfunctional metabolism of sphingolipids.

4. Pathophysiology
 A deficiency of the enzyme alpha galactosidase A due
to mutation causes a glycolipid known as
globotriaosylceramide to accumulate within the blood
vessels, other tissues, and organs.

6. Incidence
 The incidence of Fabry disease is estimated to be
between 1 in 40,000 to 1 in 120,000 live births

7. Inheritance
 Xq21.3-q22
 Genomic coordinates (GRCh37): X:100,652,778 -
100,663,000
 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.

8. Gene location:

10. Symptoms
 Pain: Extremities or GI tract (Acroparesthesia)
 Renal involvement: Proteinuria
 Cardiac manifestations: Hypertension and
cardiomyopathy
 Dermatological manifestations: Angiokeratomas,
Anhidrosis, hyperhidrosis, Raynaud's disease-like
symptoms
 Ocular manifestations: Keratopathy, cataracts,
papilloedema, macular edema, optic atrophy
 Other manifestations:Fatigue, neuropathy, tinnitus,
vertigo, nausea, chemical imbalances, and diarrhea
Stroke of unknown etiology in young adulthood.

11. Two major signs:
angiokeratoma cataract

12. Raynaud's disease-like symptoms

13. Diagnosis
 the diagnosis can usually be confirmed in males if
there is low alpha-Gal A activity in leukocytes or
plasma.
 Molecular genetic analysis of the GLA gene is the most
accurate method of diagnosis in female.
 Kidney biopsy may also be suggestive of Fabry disease
if excessive lipid buildup is noted.

14. Treatment
 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).
 The pharmaceutical company Shire manufactures
agalsidase alpha under the brand name Replagal as a
treatment for Fabry's disease.

15. Prognosis
 males was 58.2 years, compared with 74.7 years.
 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. Thanks for your
attention

17. Reffrenses:
1. http://www.uptodate.com
2. http://www.myoclinic.com
3. http://www.ncbi.nlm.nih.gov/pubmed
4.www.geneticreaserch.com
5. http://ghr.nlm.nih.gov/gene/GLA