Fabry Disease – Underestimated in the Differential Diagnosis of Multiple Sclerosis?

PLoS ONE 8(8): e71894. doi:10.1371/journal.pone.0071894

Objective: Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods: Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results: Four patients were identified as having a ‘‘possible’’ history of MS, and 7 patients as ‘‘definite’’ cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (69.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (610.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL611.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion: There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.