A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease

Inclusion Criteria

• •Cohort 1:
• •1. The patient has a documented diagnosis of Fabry disease.
• •2. The patient is sufficiently compliant with study activities to participate in this treatment plan, as judged by the Investigator.
• •3. The patient must meet current Canadian guidelines for enzyme replacement therapy for Fabry disease by meeting one of the following criteria:
• •1. Age-adjusted glomerular filtration rate (GFR) \<80 ml/min or a decline in GFR of \>10% which is sustained for 3 months and for which other causes of declining renal function have been excluded by a nephrologist or any 2 of the following:
• •* Isolated proteinuria ≥500 mg/day/1.73 m2 without other cause
• •* Nephrogenic diabetes insipidus
• •* Fanconi syndrome
• •* Hypertension
• •2. Evidence of cardiac involvement related to Fabry disease including any 2 of the following:
• •* Left ventricular (LV) wall thickness \>12 mm
• •* Left ventricular hypertrophy (LVH) by electrocardiogram (ECG); Estes ECG score must be \>5
• •* Left ventricular mass index (LVMI) by 2D echocardiogram 20% above normal for age
• •* Diastolic filling abnormalities by 2D echocardiogram or by other accepted measures of diastolic filling. E/A ration \>2.0 and deceleration time \<140 msec
• •* Increase of LV mass of at least 5 g/m2/year, with three measurements over a minimum of 12 months
• •* Increase of left atrium (LA) size on 2D echo at least 10% above normal for age. In parasternal long axis view (PLAX) \>33 mm; in four chamber view \>42 mm
• •* Cardiac conduction and rhythm abnormalities: atrioventricular (AV) block, short PR interval, left branch bundle block (LBBB), ventricular or atrial tachyarrhythmias, sinus bradycardia (in the absence of drugs with negative chronotropic activity)
• •* Delayed posterolateral left ventricular wall late enhancement on MRI as evidence of advanced cardiac disease with fibrosis
• •3. Evidence of neurological involvement related to Fabry disease including 1 of the following:
• •* Stroke or transient ischemic attack (TIA) prior to the age of 55 documented by a neurologist
• •* Acute onset unilateral hearing loss
• •* Acut monocular visual loss without other cause
• •4. Chronic, intractable diarrhea and/or abdominal pain/cramps, refractory to standard management for at least 6 months.
• •5. Chronic, intractable neuropathic pain, refractory to analgesics and standard pain management for at least 6 months.
• •Cohort 2:
• •4. Patient must have participated in Study REP001a.