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

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.

Eligibility Criteria:
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