Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by University of Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock Identifier:
First received: January 6, 2011
Last updated: April 12, 2016
Last verified: April 2016
The association of Multiple Sclerosis (MS) and Fabry disease is known from own clinical experiences as well as from case reports in the literature, where symptoms and suspicious results in the brain MRI led to the misdiagnosis of Fabry patients as MS. Remarkably, those patients almost never showed oligoclonal bands or an intrathecally derived IgG-production was wrongly assumed due to misinterpretation of CSF results. Where oligoclonal bands were present, concomitant diagnoses had to be discussed. Furthermore, those patients showed no involvement of the spinal cord, as evidenced by MRI. Beside the possible complications of a not-effective and not-necessary MS therapy, those patients are at risk of irreparable organ damage due to the delayed implementation of enzyme replacement therapy for Fabry disease.

Multiple Sclerosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Multiple Sclerosis and Fabry Disease: Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis - an Epidemiological Study

Resource links provided by NLM:

Further study details as provided by University of Rostock:

Primary Outcome Measures:
  • Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis [ Time Frame: 24 month ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
Fabry diagnostic will be done centrally: blood samples will be stored for analysis of a-galactosidase in blood, Gb3 as well as lyso-Gb3. In all cases direct analysis of the gene will be done, especially in females where due to the Lyonisation effect a-galactosidase activity might be normal in blood although the patient might suffer from Fabry disease.

Estimated Enrollment: 250
Study Start Date: January 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Patients at age 18-50 with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for MS

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. In Europe the prevalence of Fabry disease seems to be massively underrepresented.

Multiple Sclerosis (MS, Encephalomyelitis disseminata) ist the most common inflammatory disease of the central nervous system (CNS). The first clinical manifestation peaks in the 3rd-4th decade. 2.5 million Young adults are affected worldwide. In Germany the prevalence rate reaches approx. 100 patients per 100,000 inhabitants. Females are more frequently affected (2-3:1). The underlying causes of the disease are not sufficiently explored yet. The genetic backgrounds as well as environmental factors are involved. An autoimmune mediated process, driven by activated T-lymphocytes and macrophages, leads to inflammatory demyelination and axonal loss.

Magnetresonance imaging of the brain and spinal cord, evaluation of the cerebrospinal fluid to detect intrathecally derived immunoglobulin production (IgG) and a comprehensive diagnostic workup on other possible causes of the symptoms. The modern diagnostic criteria (McDonald criteria, 2001 + revisions 2005) demand the proof of the dissemination of the inflammatory process in space and time, either by clinical or radiological terms.

The evaluation of the cerebrospinal fluid aims at the confirmation of an intrathecally derived synthesis of IgG. In 98% of the patients oligoclonal bands can be detected during the course of the disease. This parameter is highly sensitive but only low specific. The diagnostic criteria allow making the diagnosis of "certain" or at least "probable" MS without the confirmation of oligoclonal bands.


Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Adult Patients at age 18-50 with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for Multiple Sclerosis

Inclusion Criteria:

  • Patients at age 18-50 years old with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for MS
  • Patients with confirmed diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria but without confirmation of oligoclonal IgG in the CSF
  • Patients with present oligoclonal IgG in the CSF but without proof of dissemination of spinal inflammatory processes in the MRI
  • Signed informed consent

Exclusion Criteria:

  • Patients being younger than 18 years or older than 50 years
  • Patients without performed MRI of the brain and spinoaxis
  • Patients with a structural change in the brain that is not caused by a chronic inflammatory disease of the CNS
  • Missing signed 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: NCT01271699

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

Universitätsklinikum Aachen, Klink für Neurologie Recruiting
Aachen, Germany, 52074
Contact: Jörg Schulz, Prof. MD    0049 2418089600   
Sub-Investigator: Simone Tauber, MD         
Kamillusklinik, Abtl. Neurologie Recruiting
Asbach, Germany, 53567
Contact: Dieter Pöhlau, MD    0049 2683 59 663    dieter.pö   
Sub-Investigator: Anka Liebezeit, MD         
Berlin Charite, Klinisches und experimentelles Forschungszentrum für Multiple Sklerose Recruiting
Berlin, Germany, 10117
Contact: Klemens Ruprecht, MD    0049 30450560374   
Principal Investigator: Klemens Ruprecht, MD         
Jüdisches Krankenhaus Berlin, Abt. Neurologie Recruiting
Berlin, Germany, 13347
Contact: Haas Judith, Prof. MD    0049 30 4994 2348   
Sub-Investigator: Marko Chatzopoulos, MD         
Sub-Investigator: Stephan Haack, MD         
HHU Düsseldorf, Klinik und Poliklinik für Neurologie Recruiting
Düsseldorf, Germany, 40225
Contact: Orhan Aktas, Prof. MD    0049 2118104169   
Sub-Investigator: Marius Ringelstein, MD         
Alfried Krupp Krankenhaus Rüttenscheid, Abt. Neurologie Recruiting
Essen, Germany, 45131
Contact: Markus Krämer, MD    0049 20143441424   
Principal Investigator: Markus Krämer, MD         
Universitätsklinikum Gießen und Marburg, Neurovaskuläre AG Recruiting
Gießen, Germany, 35392
Contact: Manfred Kaps, Prof. MD    0049 641-98540   
Sub-Investigator: Christian Tanislav, MD         
Augustahospital AnholT GmbH, Abt. Neurologie Recruiting
Isselburg, Germany, 46419
Contact: Michael Haupts, Prof. MD    0049 2874 46 430   
Sub-Investigator: Christian Haug, MD         
Universität Münster, Klinik & Poliklinik für Neurologie Recruiting
Münster, Germany, 48149
Contact: Bernd Ringelstein, Prof. MD    0049 25183 48172   
Sub-Investigator: Thomas Duning, MD         
Universität Rostock, Zentrum für Nervenheilkunde Recruiting
Rostock, Germany, 18147
Contact: Uwe Zettl, Prof. MD    0049 381494 9517   
Sub-Investigator: Alexander Winkelmann, MD         
Krankenhaus der Bamherzigen Brüder Trier, Neurologische Klinik Recruiting
Trier, Germany, 54292
Contact: Matthias Maschke, Prof. MD    0049 651 2082741   
Sub-Investigator: Christoph Klawe, MD         
Universitätsklinikum Ulm, Klinik für Neurologie Recruiting
Ulm, Germany, 89081
Contact: Hayrettin Tumani, MD    +49 731177 ext 1207   
Sub-Investigator: Simonetta Niendorf, MD         
Sub-Investigator: Florian Lauda, MD         
Universitätsklinik Würzburg, Neurologische Klinik Recruiting
Würzburg, Germany, 97080
Contact: Christoph Kleinschnitz, MD    0049 93120123488   
Sub-Investigator: Peter Kraft, MD         
Sub-Investigator: Gesa Weise, MD         
Sponsors and Collaborators
University of Rostock
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information


Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock Identifier: NCT01271699     History of Changes
Other Study ID Numbers: MS01/2011 
Study First Received: January 6, 2011
Last Updated: April 12, 2016
Health Authority: Germany: Ethics Commission

Keywords provided by University of Rostock:
Fabry Disease
Fabry´s Disease
Anderson-Fabry Disease
Multiple Sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Fabry Disease
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Immune System Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Pathologic Processes
Vascular Diseases processed this record on May 25, 2016