Registry of Fabry Disease – A Multicenter Observational Study

The purpose of this study is to compile a registry of patients with Fabry disease, an inherited metabolic disorder. In this disease, an enzyme called a-galactosidase A, which normally breaks down a lipid (fatty substance) called globotriaosylceramide (Gb3), is missing or does not function properly. As a result, Gb3 accumulates, causing problems with the kidneys, heart, nerves, and blood vessels. It is not known exactly how lipid accumulation causes these problems, but in another lipid storage disease called Gaucher disease the illness can be reversed if the accumulated lipid is removed by repeated intravenous (into a vein) infusions of the deficient enzyme.

Official Title

Registry of Fabry Disease: A Multicenter, Longitudinal Observational Study

Conditions

– Fabry Disease

Study Type

Observational

Study Design

Natural History: This registry will collect information on patients diagnosed with Fabry disease. Patients who are diagnosed with Fabry disease and receive Fabry specific treatment will be followed throughout their course of therapy. Patients diagnosed with Fabry disease who are not treated will also be followed.

Further Details

The Fabry disease registry is a voluntary and anonymous list of patients that includes information about their health and allows doctors to follow changes in their symptoms and test results over time. It also allows doctors to compare symptoms between patients who are receiving certain therapies with those who are not receiving therapy. The goals of the registry are to: – Better understand the natural history of Fabry disease, including disease variations within and between affected families;- Provide a basis for developing guidelines for disease management;- Evaluate how treatment affects the course of disease;- Provide high-quality data and analyses that will help to continuously develop better treatments.Patients of all ages with biochemical or genetic evidence of Fabry disease (i.e., individuals who have a deficiency of the enzyme a-galactosidase A or a mutation in the gene that encodes this enzyme, or both) are eligible for this study. This worldwide study will include 100 patients participating in Fabry disease studies at the NIH. These patients will come to the NIH Clinical Center only as required for participation their Fabry disease study. No additional procedures will be required for the current registry study. NIH patients will take part in the registry study for their lifetime, or as long as they are being followed at the NIH for their Fabry disease. At their regularly scheduled NIH clinic visits, participants will have routine medical procedures and examinations deemed necessary by the doctor. The results of blood and urine tests taken at these visits will be entered into the registry database. Blood tests will include information on genotype (determination of which gene mutation is responsible for the disease), a-galactosidase A levels, Gb3 levels, and creatinine. Urine tests results will include creatinine clearance (a measure of kidney function) and protein evaluation. Fabry disease is an X-linked recessive glycosphingolipid storage disorder that is caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Globotriaosylceramide (Gb3, also known as CTH), which is the glycosphingolipid substrate for this enzyme, progressively accumulates within vulnerable cells and tissues of affected patients. Renal epithelial cells, myocardial cells, dorsal root ganglia, endothelial, perithelial, and smooth muscle cells of the vascular system, and cells of the autonomic nervous system are selectively damaged by Gb3. The objectives of this registry are to:enhance the understanding of the natural history of Fabry disease, including the intra-and interfamilial variationsprovide a basis for the development of management guidelines for Fabry diseaseevaluate the impact of therapeutic intervention on the clinical course of Fabry diseaseprovide high quality data and analyses to enable the continuous improvement of Fabry disease treatmentStudy design: This registry will collect information on patients diagnosed with Fabry disease. Patients who are diagnosed with Fabry disease and receive Fabry specific treatment will be followed throughout their course of therapy. Patients diagnosed with Fabry disease who are not treated will also be followed. Outcome measures include: summary statistics for demographic and baseline characteristic data for all patients will be tabulated using the summary statistics mean, standard deviation, median, minimum, maximum, and the number of patients. The categorical variables, sex and race, will state the number and percent of patients in each category. Patients will be grouped according to whether they are receiving Replagal treatment or not. Because this study consists of a non-randomized, pre-selected population of patients, hypothesis testing may not be performed. However, any hypothesis tests performed will only be exploratory. Continuous data will be analyzed using the parametric tests such as the Student’s t-test or non-parametric test such as the Wilcoxon rank-sum test. Differences in frequencies will be subjected to the Fisher exact test. Kaplan-Meier plots showing differences in the age of onset of renal syndromes or strokes will be evaluated using the Mantel-Cox test. A p-value of less than 0.05 will be accepted as statistically significant. Distance among aligned sequences as well as genetic distance among patients in a family will be presented.

Study Start

Eligibility & Criteria

Genders Eligible for Study: Both Criteria INCLUSION CRITERIA:This registry is open for all patients of all ages, male and female, with a confirmed diagnosis of Fabry disease.EXCLUSION CRITERIA:There are no clinical exclusion criteria.Patients who are unwilling to give informed consent.

Total Enrolment

100

Contact Details

[1] National Institute of Neurological Disorders and Stroke (NINDS) (US)