Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Fabry Disease; Sclerosis
Study type: Observational

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.
    

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.
    

Observational model: Cohort
Time perspective: Retrospective
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
      
Biospecimen 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.
    
Keywords: Fabry Disease; Fabry´s Disease; Anderson-Fabry Disease; Multiple Sclerosis