Fabry Disease

By

Farshid mokhberi

Shahid beheshti University of Medical Sciences

Fabry disease

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.

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.

Incidence

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

InheritanceXq21.3-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.

Gene location:

SymptomsPain: Extremities or GI tract (Acroparesthesia)Renal involvement: ProteinuriaCardiac manifestations: Hypertension and

cardiomyopathyDermatological 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.

Two major signs:angiokeratoma cataract

Raynaud's disease-like symptoms

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.

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.

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.

Thanks for your attention

Reffrenses:1. http://www.uptodate.com2. http://www.myoclinic.com3. http://www.ncbi.nlm.nih.gov/pubmed4.www.geneticreaserch.com5. http://ghr.nlm.nih.gov/gene/GLA