International Center for Fabry Disease
We continue to provide comprehensive evaluation of patients and carriers of Fabry disease on our General Clinical Research Center (GCRC). The GCRC at the Icahn School of Medicine is an inpatient and outpatient unit that is separate from the rest of the hospital and is staffed by nurses who are specifically educated about Fabry disease.
A complete evaluation of patients typically requires a stay of four to five weekdays during which consultations with experts in cardiology, renal disease, neurology, ophthalmology, pulmonary, ear nose and throat and pain are obtained. Each member of this team of consultants has a particular interest in Fabry disease and they are all committed to providing state-of-the-art care to our patients. Laboratory tests also are performed during a stay on the GCRC and include analyses of peripheral blood and urine and the performance of a variety of special studies including magnetic resonance imaging (MRI), renal sonogram, echo cardiogram, and pulmonary function testing. At the conclusion of these studies, a complete discussion of the results and their interpretation is held during a consultation with the patient and family, and specific recommendations for current and future management are made.
We cloned the gene for a-galactosidase A, the enzyme deficient in Fabry disease, and have identified specific mutations within the gene that result in this disorder. These include small deletions of portions of the gene and point mutations, which are single mistakes in the gene that can be likened to the mistake one would find in a misspelled word. For most families, it is now possible to identify the mutation that is present in their a-galactosidase A gene permitting the diagnosis of Fabry disease and the identification of carrier females by the direct detection of the molecular defect. These analyses also have been useful in increasing our understanding of the underlying defects that result in Fabry disease.
Prenatal diagnosis is available in our laboratory for all female carriers of Fabry disease who have a 25% risk in each pregnancy of having an affected male. These studies require a sample of fetally derived tissue that can be obtained either by chorionic villus sampling (CVS), which can be performed as early as the ninth week of pregnancy, or by amniocentesis, which is performed at approximately 16 weeks after the last menstrual period. Besides the fact that it can be performed very early in pregnancy, CVS has the advantage of providing results within 2 to 3 days, if an adequate sample is obtained, whereas amniocentesis results are not available for at least 10 days. Regardless of the method chosen, it is recommended that patients come to Mount Sinai for their procedure. However, if this presents an extreme hardship, other arrangements can be made after discussion with our Center. Call the toll free number to speak with our genetic counselor or one of our expert physicians (1-866-FABRY MD).
Prospects for Therapy
Through ongoing efforts in our laboratory, we have been involved in the development of enzyme replacement therapy for Fabry disease. We cloned the gene for a-galactosidase A, achieved its production in cells grown in the Laboratory, and performed preclinical studies in "Fabry Mice". These animal studies provided the rationale for human clinical trials. In 1998, an FDA reviewed Phase 1/ 2 clinical trial was performed at Mount Sinai with 15 Fabry Patients. This study evaluated various enzyme doses and their dose-response clearance of the accumulated glycolipid in key tissues including the blood, skin, kidneys, heart, and liver. Based on the results, an FDA-reviewed Phase 3 clinical trial was conducted. This was a double-blind placebo-controlled, randomized multicenter study involving 58 patients with Fabry disease in four countries (US, France, England, and the Netherlands). This study achieved its primary goal of demonstrating that the enzyme effectively cleared the accumulated glycolipid from key cells in the kidney, as well as from cells in the skin and heart. Currently, we are recruiting patients for a Phase 4 clinical trial which is being conducted at Mount Sinai and at other sites throughout the world.