Clinical Trial: Myocardial Affectation in Patients With Fabry Disease Without Phenotypic Manifestation. Diagnostic Value of Biomarkers
Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational
Official Title: Myocardial Affectation in Patients With Fabry Disease Without Phenotypic Manifestation. Diagnostic Value of Biomarkers
Brief Summary: The cardiac variant of the Fabry disease is a rare cardiomyopathy affecting 1/50000 individuals in general population. It is generally diagnosed in advanced stages of the disease, because it presents clinical features very similar to the hypertrophic cardiomyopathy ones, making difficult the correct diagnosis. In Fabry disease there is a remodeling process of the myocardial interstitium and apoptosis of myocytes which leads to fibrosis development and later systolic dysfunction. The investigators propose to evaluate the utility of several biomarkers in the diagnosis of this cardiomyopathy, to facilitate the early diagnosis, which is clue to establish early enzyme replacement therapy or intensify the patients' follow up. In order to achieve this objective, the investigators will analyze markers of endothelial dysfunction, fibrosis and apoptosis in peripheral blood samples of patients carrying the mutation but without clinical manifestations and the investigators will compare their levels with dose obtained from two different control groups: diagnosed patients presenting clinical manifestations or index cases and healthy controls without carrying the mutation.
Detailed Summary:
Fabry disease is an X-linked recessive disease, affecting lysosomal storage with a variable phenotype characterized by the accumulation of glycosphingolipids in several tissues. It has been described more than 200 mutations in the alfa-galactosidase A (GLA) gene which cause Fabry disease. Nowadays, the treatment of Fabry disease consists of enzyme replacement therapy (ERT) which development has shown a reversal of abnormal accumulation of glycosphingolipids in different tissues and a clinical improvement or stabilization (1). Unlike classic systemic Fabry disease with multiple organ affectation, the cardiac variant of the disease is characterized by myocardial hypertrophy. Hence, cardiac Fabry variant is defined as a storage myocyte disorder mimicking the clinical features of the hypertrophic cardiomyopathy (HCM)(2).
The gold standard for the diagnosis of Fabry disease is the electron microscopy evaluation of cardiac samples obtained from endomyocardial biopsy (2), although it has been published that the determination of the alfa-galactosidase activity in plasma of patients diagnosed of Fabry disease, followed by sequencing of the GLA gene in those individuals with low activity level is a good non-invasive diagnostic method which allows the identification of the disease carriers and the early start of the enzymatic replacement therapy (3).
Due to the similarity between clinical characteristics of both diseases and to the extraordinary low incidence of the Fabry disease, the biopsy execution is rarely carried out for diagnosis. Hence, it has been speculated that a higher disease incidence should exist hidden among patients presenting with clinical symptoms of HCM. Several studies have evaluated the incidence of the Fabry disease among patients diagnosed of HCM, finding out that even 8-10% of these patients actually presente
Sponsor: Francisco Marín Ortuño
Current Primary Outcome:
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Information By: Hospital Universitario Virgen de la Arrixaca
Dates:
Date Received: September 26, 2011
Date Started: October 2011
Date Completion: April 2013
Last Updated: September 27, 2011
Last Verified: September 2011
