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

NCT01271699 | Completed DMC

• 1 other identifier: MS01/2011
• Study Type: observational
• Target: 250
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Multiple Sclerosis

Keywords

Fabry Disease; Fabry´s Disease; Anderson-Fabry Disease; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

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

  24 month

Study Arms (1)

Observation

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CENTOGENE GmbH Rostock: lead

Related Publications (11)

• 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.

  PMID: 19150871 BACKGROUND

• Falke K, Buttner 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.

  PMID: 18931853 BACKGROUND

• Fellgiebel A, Keller I, Marin D, Muller MJ, Schermuly I, Yakushev I, Albrecht J, Bellhauser 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.

  PMID: 19122032 BACKGROUND

• 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. doi: 10.1097/gim.0b013e31802d8321.

  PMID: 17224688 BACKGROUND

• Rolfs A, Bottcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Lohr 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. doi: 10.1016/S0140-6736(05)67635-0.

  PMID: 16298216 BACKGROUND

• 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. doi: 10.1002/ana.1032.

  PMID: 11456302 BACKGROUND

• 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. doi: 10.1002/ana.20703.

  PMID: 16283615 BACKGROUND

• 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. doi: 10.1007/s00115-002-1328-x. German.

  PMID: 12243005 BACKGROUND

• Callegaro D, Kaimen-Maciel DR. Fabry's disease as a differential diagnosis of MS. Int MS J. 2006 Jan;13(1):27-30.

  PMID: 16420782 BACKGROUND

• Saip S, Uluduz D, Erkol G. Fabry disease mimicking multiple sclerosis. Clin Neurol Neurosurg. 2007 May;109(4):361-3. doi: 10.1016/j.clineuro.2006.12.006. Epub 2007 Jan 17.

  PMID: 17234336 BACKGROUND

• 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.

  PMID: 18632784 BACKGROUND

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.

MeSH Terms

Conditions

Multiple Sclerosis; Fabry Disease

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Sphingolipidoses; 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Arndt Rolfs, MD

  CENTOGENE GmbH Rostock

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2011
• First Posted: January 7, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 9, 2021

Record last verified: 2020-04