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

This study is currently recruiting participants.
Verified November 2013 by University of Rostock
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01271699
First received: January 6, 2011
Last updated: November 7, 2013
Last verified: November 2013

January 6, 2011
November 7, 2013
January 2011
February 2015   (final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT01271699 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis
Multiple Sclerosis and Fabry Disease: Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis - an Epidemiological Study

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Retrospective
Not Provided
Retention:   Samples With DNA
Description:

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.

Probability Sample

Adult Patients at age 18-50 with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for Multiple Sclerosis

Multiple Sclerosis
Not Provided
Observation
Patients at age 18-50 with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for MS

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
250
March 2015
February 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 50 Years
No
Contact: Arndt Rolfs, MD 49-381-494 ext 9540 arndt.rolfs@med.uni-rostock.de
Contact: Sabine Roesner 49-381-494 ext 4797 sabine.roesner@med.uni-rostock.de
Germany
 
NCT01271699
MS01/2011
Yes
Prof. Dr. Arndt Rolfs, University of Rostock
University of Rostock
Not Provided
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
University of Rostock
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP