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Fabry and Cardiomyopathy (FaCard) Epidemiological Study for the Analysis of Biomarkers and the Clinical Course of Patients With Fabry Disease and the N215S-mutation

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock Identifier:
First received: September 6, 2011
Last updated: June 3, 2014
Last verified: June 2014

Primary objective and endpoint is the analysis of the long-term course of lyso-Gb3 and its clinical correlation to the progression of the cardiomyopathy in N215S-Fabry patients.

Cerebrovascular Accident
Stroke, Acute
Cerebral Stroke

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Fabry and Cardiomyopathy (FaCard) Epidemiological Study for the Analysis of Biomarkers and the Clinical Course of Patients With Fabry Disease and the N215S-mutation AN INTERNATIONAL,MULTICENTER, EPIDEMIOLOGICAL STUDY

Resource links provided by NLM:

Further study details as provided by University of Rostock:

Biospecimen Retention:   Samples With DNA

The laboratory examinations of the blood samples for measuring the lyso-Gb3-level will be done at the Laboratory of the Albrecht-Kossel-Institute, University of Rostock in collaboration with associated diagnostic laboratory partners. This laboratory offers an existing infrastructure, a highly standardized quality of the workflow, a short examination time of the samples and a long period of experiences in the assessment of the biological impact of mutations and polymorphism, as evidenced recently in the sifap1-study.

Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
All Patients with a diagnosis of Fabry disease with N215S

Detailed Description:

Fabry disease is an X-linked lysosomal disorder that leads to excessive deposition of neutral glycosphingolipids in the vascular endothelium of several organs in the body. Progressive endothelial accumulation of glycosphingolipids accounts for the associated clinical abnormalities of skin, eye, kidney, heart, brain, and peripheral nervous system. Fabry disease manifesting predominantly in men. Female heterozygotes also present with features of Fabry disease. It is suggested that the mean age of hemizygotic men at the onset of symptomatic stroke is 29 - 34 years. The mean age of female heterozygotes at the onset of symptomatic strokes is 40 - 43 years.In Europe the prevalence of Fabry disease seems to be massively underrepresented; actual textbooks describe 1 per 40.000. However, recent data (Lin HY, et al., 2009) demonstrate the identification of eight different mutations in the alpha-galactosidase A (alpha-Gal A) gene in 110 027 newborns who were screened by assaying the alpha-Gal A activity followed by genetic analysis. Hwu and co-workers (2009) have shown in 90,288 male newborns screened for Fabry disease that 73 males had GLA gene mutations. Surprisingly, 86% had the c.936+919G>A (also called IVS4+919G>A) splice mutation. In contrast, screening 81,689 females detected two heterozygotes. Summarizing, newborn screening identified a surprisingly high frequency of Taiwanese males with Fabry disease (approximately 1 in 1,250), 86% having the IVS4+919G>A mutation previously found in later-onset cardiac phenotype patients.The late-onset mutation N215S is discussed to be a so-called cardiac variant (Perry Elliott, 2006; Eng et al., 1993, Sachdev et al., 2002). The prevalence of most mutations is low, i.e. Fabry disease spontaneously and individually inheriting so-called private mutations. However, there are some mutations that occur more frequent. Besides for instance R112H, A143T and R227X, also N215S belongs to this group (Dobrovolny et al., ASHG Abstract, 2008). The enzyme activity is only moderately affected, but hemizygous patients display a clearly decreased activity in leucocytes and fibroblasts.

In 2005, Young and colleagues (Acta Paediatr Suppl.) concluded that Gb3 is not an ideal biomarker using the example of N215S. All heterozygotes were unconspicuous and only 50% of the examined hemizygotes had increased levels. However, globotraosylceramid (lyso Gb3) seems to reveal all (genetically) found patients with a pathologically elevated level (with a mean of 1,17ng/ml (females) and 2,43ng/ml (males) respectively).

In a case study from 2004 (Meehan et al., American Journal of Kidney Diseases) was shown that a hemizygous male 75 years of age had a renal manifestation of mild proteinuria and a mildly decreased renal function due to high Gb3 accumulation in podocytes, to a lesser extent in tubular endothelial cells. Furthermore, he had mild congestive heart failure, a reduced left ventricular ejection fraction, and hypercholesterolemia. Thus, it is obvious that in Fabry patients with the N215S mutation disease progression can be mono- to oligosymptomatic, but show a tendency for the cardiac and renal phenotype rather than classical manifestation.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

All Patients with a diagnosis of Fabry disease with N215S


Inclusion Criteria:

  • All patients of both gender from 18 years of age with a diagnosis of Fabry disease with the mutation N215S
  • Written informed consent from patient

Exclusion Criteria:

  • Patients without a diagnosis of Fabry disease
  • No written informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01429597

Contact: Arndt Rolfs, MD 49-381-494 ext 9540
Contact: Sabine Roesner 49-381-494 ext 4797

University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration Recruiting
Rostock, Germany, 18147
Contact: Sabine Roesner    49-381-494 ext 4797   
Principal Investigator: Arndt Rolfs, MD         
Sponsors and Collaborators
University of Rostock
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

No publications provided

Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock Identifier: NCT01429597     History of Changes
Other Study ID Numbers: FaCard06/2011
Study First Received: September 6, 2011
Last Updated: June 3, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by University of Rostock:
Cerebrovascular Accident
Cerebrovascular Accident, Acute
Fabry Disease
Fabry´s Disease
Anderson-Fabry Disease
CVA (Cerebrovascular Accident)
Stroke, Acute
Cerebral Stroke

Additional relevant MeSH terms:
Cerebral Infarction
Fabry Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heart Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Vascular Diseases processed this record on November 20, 2014