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

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Abstract

Background

F abry disease (FD) is an X-linked lysosomal storage disorder with accumulation of globotriosylceramide, causing neurologic involvement mainly as acroparesthesias and cerebrovascular disease. Aseptic meningitis has been reported in 11 patients with FD, but no prior study has correlated alpha-galactosidase (GLA) specific variants with meningitis. We present in this manuscript a family in which a novel GLA pathogenic variant was associated with aseptic meningitis in 2 of 5 family members.

Methods

This study began with identifying the proband, then screening family members for FD symptoms and evaluating symptomatic individuals for genetic and biochemical status. All patients underwent magnetic resonance imaging, and those with headache underwent cerebrospinal fluid (CSF) analysis.

Results

Five patients (3 females) from a single family were included in this study. Mean age at diagnosis was 20.6 years. Two patients (40%) had aseptic meningitis; one of them also had cerebrovascular events. C-reactive protein and erythrocyte sedimentation rate were elevated during aseptic meningitis episodes. Both patients responded to intravenous methylprednisolone with resolution of fever, headache, and vomiting. One of them recurred and needed chronic immunosuppression with azathioprine.

Conclusion

We described aseptic meningitis in a family with a novel GLA variant. Meningitis might be a common phenomenon in FD and not a particularity of this variant. Understanding the mechanisms underlying meningitis and its association with cerebrovascular events may lead to a new paradigm of treatment for stroke in these patients. Further prospective studies with CSF collection in patients with FD and recurrent headache could help to elucidate this question.

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Acknowledgements

The author Pedro Braga-Neto received funding from the Brazilian National Council for Scientific and Technological Development (CNPq) as research grant funding (productivity scholarship).

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Authors and Affiliations

  1. Division of Neurology, Department of Clinical Medicine, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, Brazil

    Paulo Ribeiro Nóbrega, Deborah Moreira Rangel & Pedro Braga-Neto

  2. Neurogenetics Unit, Department of Neurology, University of São Paulo School of Medicine, São Paulo, Brazil

    Paulo Ribeiro Nóbrega, Anderson Rodrigues Brandão de Paiva & Fernando Kok

  3. UNICHRISTUS University Center, Ceará, Brazil

    João Lucas Araújo Morais, Alisson Dantas de Medeiros & Beatrice Araújo Duarte

  4. Neurology Department, Hospital Geral de Fortaleza, Ceará, Brazil

    Alliane Milliane Ferreira, Alisson Dantas de Medeiros, Deborah Moreira Rangel, Fabrício Oliveira Lima & Fernanda Martins Maia Carvalho

  5. Department of Clinical Medicine, Universidade de Fortaleza, Ceará, Brazil

    Alliane Milliane Ferreira, Luciana Paim-Marques & Fernanda Martins Maia Carvalho

  6. Mendelics Genomic Analysis, São Paulo, Brazil

    Fernando Kok

  7. Hospital Infantil Albert Sabin, Ceará, Brazil

    André Luiz Santos Pessoa

  8. Center of Health Sciences, Universidade Estadual do Ceará, Fortaleza, Brazil

    Pedro Braga-Neto

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  1. Paulo Ribeiro Nóbrega
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Contributions

Paulo Ribeiro Nóbrega: conceptualization (lead), data curation (lead), project administration (lead), writing—original draft (lead), and writing—review and editing (lead). João Lucas Araújo Morais: data curation (equal), formal analysis (equal), investigation(equal), and writing—original draft (equal). Alliane Milliane Ferreira: data curation (equal), investigation (equal), visualization (equal), and writing—review and editing (equal). Alisson Dantas de Medeiros: conceptualization (equal), data curation (equal), formal analysis (equal), and writing—review and editing (supporting). Beatrice Araújo Duarte: writing—review and editing (equal). Deborah Moreira Rangel: data curation (equal), formal analysis (equal), investigation (equal), and writing—original draft (equal). Fabrício Oliveira Lima: data curation (equal), formal analysis (equal), and investigation (equal). Anderson Rodrigues Brandão de Paiva: data curation (equal), writing—original draft (equal), and writing—review and editing (equal). Fernando Kok: data curation (equal), formal analysis (equal), investigation (equal), supervision (equal), and writing—review and editing (equal). Luciana Paim-Marques: formal analysis (equal), investigation (equal), supervision (equal), and writing—review and editing (equal). André Luis Santos Pessoa: data curation (equal), writing—original draft (equal), and writing—review and editing (equal). Pedro Braga-Neto: data curation (equal), formal analysis (equal), investigation (equal), supervision (equal), and writing—review and editing (equal). Fernanda Martins Maia Carvalho: conceptualization (lead), data curation (lead), formal analysis (equal), investigation (lead), supervision (lead), and writing—review and editing (lead).

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Correspondence to Pedro Braga-Neto.

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Nóbrega, P.R., Morais, J.L.A., Ferreira, A.M. et al. Aseptic meningitis in Fabry disease due to a novel GLA variant: an expanded phenotype?. Neurol Sci 44, 319–327 (2023). https://doi.org/10.1007/s10072-022-06388-y

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