Fabry disease, an x-linked recessive lysosomal storage disease (LSD) is commonly recognized as a cause of renal failure in involved men and more recently recognized in women too. Women are involved in significant numbers and with complications, as are men, of vascular disease. This manifests as unexpected strokes in young adults. We have morphologic evidence that storage-endotheliopathy induced microvascular disease is the cause of cardiopathy and of cryptogenic strokes, and that storage endotheliopathy starts in early life, probably before birth. Based on our earlier work with other endotheliopathies such as diabetes mellitus, Susac syndrome, and hypertension, we will find and study patients using unique methods, neuro-retinal fluorescein angiography (NRFA), that we have developed for this purpose. These methods include NRFA to demonstrate capillary perfusion in the optic nerve head and retinal quadrants. We anticipate, based on our earlier experience with other endotheliopathies, that we will show more vascular pathology earlier than previously reported. Using epidemiologic and genetic tools we will find more patients than previously known or expected. It will offer opportunity for earlier diagnosis, prognosis, and response to enzyme replacement therapy.

We hypothesize that Fabry disease is a poorly recognized and poorly characterized cause of microvascular disease and cryptogenic strokes in young women and men. Neuroretinal capillary perfusion abnormalities in Fabry disease will be predictive of equivalent vascular disease in kidney, heart, brain and other organs, and further that it will be responsive to change induced by enzyme replacement therapy treatment.

Specific Aims

Specific Aim 1. To demonstrate the specificity and sensitivity of the diagnostic capabilities of a neuroretinal examination which includes slit lamp and fundoscopy, and NRFA for the diagnosis of Fabry disease on a subject population of identified FD patients.

Specific Aim 2. To show capillary perfusion abnormalities in optic nerve and retina using neuroretinal fluorescein angiography in patients with Fabry disease and compare these to renal (measured by GFR).

Specific Aim 3. To show that the change in capillary perfusion studies when compared to baseline in response to enzyme replacement therapy treatment over time, as a manifestation of tissue burden and prognosis is a more sensitive biomarker of the extent of patient disease than corneal keratopathy.

Inclusion Criteria:

• Fabry patient
• evidence of angiopathy (renal, cardiac, or ocular)
• Patients above the age of 18

Exclusion Criteria:

• Patients unable or unwilling to provide written informed consent will not be recruited
• Patients who are below the age of 18
• Patients who have not or will not be undergoing Fluorescein angiography
• Allergy to fluorescein
• Pregnant women and fetuses are exclude from the study due to risks related to fluorescein and no direct benefit to the pregnant woman and fetus

Initially any Fabry patient, age 18 and above who has a confirmed diagnosis of Fabry disease by previously identifying plasma or leukocyte α-galactosidase A (α-gal A) deficiency, will be recruited from all participating physician practices. Those who present with evidence of angiopathy (with specific attention to the target organs: renal, cardiac, or ocular) will be recruited for the study.