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Background: Fabry disease (OMIM 301 500) is an X-linked lysosomal storage disease. Neurological symptoms in Fabry disease mainly include stroke, acroparesthesia, cranial nerve palsies and autonomic dysfunction. We report on aseptic meningitis in Fabry patients., Methods: Clinical analysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analysed in three cases of meningitis associated with Fabry disease., Findings: Mean age at meningitis onset was 26.6 (24-28) years. Headache was present in all cases and fever in two cases. Meningitis was always diagnosed before Fabry disease. A familial history of Fabry disease was present in two cases. Non-neurological symptoms caused by Fabry disease were present in all cases. All patients also suffered stroke and sensorineural hearing loss. Cerebrospinal fluid (CSF) analysis showed pleocytosis (mean, 36; range: 8-76 cells/mm(3)) and a high protein level (mean, 63; range, 47-70 mg/dl). C-reactive protein blood levels and erythrocyte sedimentation rate were raised. Diagnosis was assessed by low alpha-galactosidase A dosage and/or gene mutation analysis in all cases. All patients were treated with enzyme replacement therapy (ERT). In two cases, lumbar puncture was repeatedly performed and there was no normalisation of CSF under ERT alone, at 9 and 24 months of follow-up, respectively. One patient who suffered intracranial hypertension was treated efficiently with steroids, associated with azathioprine. The fact that Fabry disease could be an auto-inflammatory disorder is discussed., Interpretation: Fabry disease may cause aseptic meningitis.

Enzyme replacement therapy (ERT) has been used to treat Fabry disease - a progressive lysosomal storage disorder - since 2001. Two preparations of the enzyme alpha-galactosidase A are available in Europe: agalsidase alpha, produced in a human cell line, and agalsidase beta, produced in Chinese hamster ovary cells. To review critically the published evidence for the clinical efficacy of these two enzyme preparations. A systematic literature search was undertaken to identify open or randomised controlled trials published on Fabry disease since 2001. Eleven trials fulfilled the criteria for inclusion in this review, of a total of 586 references on Fabry disease. To date, no direct comparisons exists between the two available enzyme preparations. Significant clinical benefits compared with placebo, however, have been demonstrated with ERT, with positive effects on the heart, kidneys, nervous system and quality of life. The quality of most of these publications was less than optimal. Further prospective studies are required to confirm the long-term clinical benefits of ERT. More studies are also needed on the effects of ERT in women and on the use of ERT early in the course of Fabry disease, to prevent organ damage. Large national and international outcomes databases will also be invaluable in evaluating treatment effects and safety.