Aseptic meningitis in Fabry disease due to a novel GLA variant: an expanded phenotype?

Neurol Sci. 2023 Jan;44(1):319-327. doi: 10.1007/s10072-022-06388-y.

PMID: 36094773

Paulo Ribeiro Nóbrega, João Lucas Araújo Morais, Alliane Milliane Ferreira

Highlights: This paper presents a family in which a novel GLA pathogenic variant was associated with aseptic meningitis in 2 of 5 family members.

Abstract:

Background: A lysosomal storage disorder with accumulation of globotriosylceramide known as Fabry disease (FD) primarily affects the nervous system by generating acroparesthesias and cerebrovascular disease. Eleven patients with FD have been reported to have developed aseptic meningitis, although no previous research has linked this condition to variants in alpha-galactosidase (GLA). In this paper, a family is described in which two out of five members experienced aseptic meningitis due to a novel GLA pathogenic variant.

Methods: This investigation started with the identification of the proband, followed by a family member screening for FD symptoms and a genetic and biochemical assessment of symptomatic individuals. Every patient had a magnetic resonance imaging (MRI) scan, and those who had headaches also had their cerebrospinal fluid (CSF) examined.

Results: The five patients in this study, three of whom were female, came from a single family. At diagnosis, the average age was 20.6 years. Aseptic meningitis affected two patients (40%) and one of them also experienced cerebrovascular events. Aseptic meningitis episodes were associated with increased levels of C-reactive protein and erythrocyte sedimentation rate. With the administration of methylprednisolone intravenously, the symptoms of vomiting, headache, and fever in both patients improved. One of them recurred and required azathioprine for long-term immunosuppression.

Conclusion: With a new GLA variant, aseptic meningitis is described in a family. Meningitis may be a typical FD occurrence and not unique to this type. The mechanisms underlying meningitis and its link to cerebrovascular events may be better understood, which could result in a new paradigm for treating stroke in these patients. This matter might be clarified by additional prospective trials using CSF collection in patients with FD and recurrent headache.

Keywords: Enzyme replacement therapy, Fabry disease, Inflammation, Meningitis, Stroke