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

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: January 7, 2011
Last Update Posted: February 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
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 Prof. Dr. Arndt Rolfs, 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 ]

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.

Enrollment: 250
Study Start Date: January 2011
Study Completion Date: January 2017
Primary Completion Date: January 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.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01271699

Universitätsklinikum Aachen, Klink für Neurologie
Aachen, Germany, 52074
Kamillusklinik, Abtl. Neurologie
Asbach, Germany, 53567
Berlin Charite, Klinisches und experimentelles Forschungszentrum für Multiple Sklerose
Berlin, Germany, 10117
Jüdisches Krankenhaus Berlin, Abt. Neurologie
Berlin, Germany, 13347
HHU Düsseldorf, Klinik und Poliklinik für Neurologie
Düsseldorf, Germany, 40225
Alfried Krupp Krankenhaus Rüttenscheid, Abt. Neurologie
Essen, Germany, 45131
Universitätsklinikum Gießen und Marburg, Neurovaskuläre AG
Gießen, Germany, 35392
Augustahospital AnholT GmbH, Abt. Neurologie
Isselburg, Germany, 46419
Universität Münster, Klinik & Poliklinik für Neurologie
Münster, Germany, 48149
Universität Rostock, Zentrum für Nervenheilkunde
Rostock, Germany, 18147
Krankenhaus der Bamherzigen Brüder Trier, Neurologische Klinik
Trier, Germany, 54292
Universitätsklinikum Ulm, Klinik für Neurologie
Ulm, Germany, 89081
Universitätsklinik Würzburg, Neurologische Klinik
Würzburg, Germany, 97080
Sponsors and Collaborators
University of Rostock
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Sims K, Politei J, Banikazemi M, Lee P. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke. 2009 Mar;40(3):788-94. doi: 10.1161/STROKEAHA.108.526293. Epub 2009 Jan 15.
Falke K, Büttner A, Schittkowski M, Stachs O, Kraak R, Zhivov A, Rolfs A, Guthoff R. The microstructure of cornea verticillata in Fabry disease and amiodarone-induced keratopathy: a confocal laser-scanning microscopy study. Graefes Arch Clin Exp Ophthalmol. 2009 Apr;247(4):523-34. doi: 10.1007/s00417-008-0962-9. Epub 2008 Oct 18.
Fellgiebel A, Keller I, Marin D, Müller MJ, Schermuly I, Yakushev I, Albrecht J, Bellhäuser H, Kinateder M, Beck M, Stoeter P. Diagnostic utility of different MRI and MR angiography measures in Fabry disease. Neurology. 2009 Jan 6;72(1):63-8. doi: 10.1212/01.wnl.0000338566.54190.8a.
Wang RY, Lelis A, Mirocha J, Wilcox WR. Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007 Jan;9(1):34-45.
Rolfs A, Böttcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Löhr M, Harzer K, Strauss U, Pahnke J, Grossmann A, Benecke R. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005 Nov 19;366(9499):1794-6. Erratum in: Lancet. 2006 Dec 23;368(9554):2210.
McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121-7.
Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. Review.
Rieckmann P, Toyka KV; Multiple Sclerosis Therapy Consensus Group. [Immunomodulatory staged therapy of multiple sclerosis. New aspects and practical applications, March 2002]. Nervenarzt. 2002 Jun;73(6):556-63. Review. German.
Callegaro D, Kaimen-Maciel DR. Fabry's disease as a differential diagnosis of MS. Int MS J. 2006 Jan;13(1):27-30.
Saip S, Uluduz D, Erkol G. Fabry disease mimicking multiple sclerosis. Clin Neurol Neurosurg. 2007 May;109(4):361-3. Epub 2007 Jan 17.
Invernizzi P, Bonometti MA, Turri E, Benedetti MD, Salviati A. A case of Fabry disease with central nervous system (CNS) demyelinating lesions: a double trouble? Mult Scler. 2008 Aug;14(7):1003-6. doi: 10.1177/1352458508092355. Epub 2008 Jul 16.

Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier: NCT01271699     History of Changes
Other Study ID Numbers: MS01/2011
First Submitted: January 6, 2011
First Posted: January 7, 2011
Last Update Posted: February 17, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Prof. Dr. Arndt Rolfs, University of Rostock:
Fabry Disease
Fabry´s Disease
Anderson-Fabry Disease
Multiple Sclerosis

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

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