What is Fabry Disease?

• X-linked recessive lysosomal storage disorder
• Deficiency of a-galactosidase A (Also termed ceramide trihexosidase), resulting in the progressive accumulation of globotriaosylceramide (or GL3) paricularly in the vascular endothelium.
• Major organ involved:
  • Kidney
  • Heart
  • Central and perpheral nervous system

Clinical Manifestations

• Paresthesias and burning pain in fee and hands radiating inward
• Hypohidrosis/ anhidrosis
• Hat, cold or exercise intolerance
• Fatigue
• Angiokeratomas
• Whorl like structures in the cornea when examined with a slit lamp microscopy
• Recurrent fever for no reason
• Gastrointestinal: Diarrhea
• Renal involvemente: varying from mild proteinuria to renal failure
• Cardiac manifestations: Left ventricular hypertrophy, valvular disease (especially mitral insufficiency), coronary artery disease and conduction abnormalitiies
• Cerebrovascular manifestations: early stroke, TIA's, white matter lesions, dizziness or vertifgo and hemiparesis

Pathogenesis of Fabry

• Major manifestations of Fabry disease result from the progressive accumulation of GL3 in:
• The vascular endothelium, leading to ischemia and infarction, especially in the kidney, heart and brain
• The podocytes leading to proteinuria
• The cardiomyocytes causing cardiac hypertorophy and coduction abnormalities

Diagnosis of Fabry - Observational

• Corneal Dystrophy
  • Corneal Involvement greater than 80%
  • Slit lamp microscopy
• Cutaneous lesions
  • Biopsy – lipid inclusion/dilation of capillaries
• Family History/Pedigree
• Extremely important for all families to have a pedigree performed

Diagnosis of Fabry - Definitive

• Enzyme assay (Males) – alpha Gal A activity
• Urine exam – birefringent lipid/malteses crosses
• Mutation Analysis (Females, Lyonization)

Treatment Options

• Pain
  • Prophylactic anticonvulsant/narcotics
• Diarrhea
  • Pancrelipase/diet
• Enzyme Replacement Therapy
  • Addresses underlying cause of disorder

“If you suspect one of your patients may have Fabry disease, here is a list of the labs that provide both the enzyme testing for males and the DNA analysis for females”.

Testing Labs

Lab: Genzyme Genetics
Phone: 800- 848-4436
Tests: Gaucher Enzyme/DNA, Fabry Enzyme/DNA, Chitotriosidase, TRAP, ACE

Lab: Mount Sinai School of Medicine
Phone: 1-866-322-7963
Tests: Gaucher Enzyme/DNA, Fabry Enzyme/DNA, Chitotriosidase, TRAP, ACE
Contact: Donna Doheny – Direct Line : 1-212-659-6779

Lab : New York University School of Medicine
Phone: 1-212-263-8344
Tests: Gaucher Enzyme/DNA, Fabry Enzyme/DNA, Chitotriosidase, TRAP, ACE

Lab: Baylor School of Medicine
Phone: 1-800-411-4363
Tests: Gaucher Enzyme/DNA, Fabry Enzyme/DNA

Lab: Cincinnati Children’s Hospital and Medical Center
Phone: 1-513-636-4507
Tests: Gaucher Enzyme/DNA, Fabry Enzyme/DNA, Chitotriosidase, TRAP, ACE

Lab: Yale University
Phone: 1-203-785-3412

This list is not exhaustive and other labs may be found at www.genetests.org

If you have Fabry disease and have not been evaluated, or have not had a family pedigree performed, you should contact one of the treatment centers located throughout New England for an evaluation.