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Erschienen in:

12.09.2022 | Original Article

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

verfasst von: Paulo Ribeiro Nóbrega, João Lucas Araújo Morais, Alliane Milliane Ferreira, Alisson Dantas de Medeiros, Beatrice Araújo Duarte, Deborah Moreira Rangel, Fabrício Oliveira Lima, Anderson Rodrigues Brandão de Paiva, Luciana Paim-Marques, Fernando Kok, André Luiz Santos Pessoa, Pedro Braga-Neto, Fernanda Martins Maia Carvalho

Erschienen in: Neurological Sciences | Ausgabe 1/2023

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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.
Literatur
2.
Zurück zum Zitat Sweeley CC, Klionsky B (1963) Fabry’s disease: classification as a sphingolipidosis and partial characterization of a novel glycolipid. J Biol Chem 238:3148–3150CrossRef Sweeley CC, Klionsky B (1963) Fabry’s disease: classification as a sphingolipidosis and partial characterization of a novel glycolipid. J Biol Chem 238:3148–3150CrossRef
7.
8.
Zurück zum Zitat Chien YH, Lee NC, Chiang SC, Desnick RJ, Hwu WL (2012) Fabry disease: incidence of the common later-onset α-galactosidase A IVS4+919G→A mutation in Taiwanese newborns—superiority of DNA-based to enzyme-based newborn screening for common mutations. Mol Med 18(1):780–784. https://doi.org/10.2119/molmed.2012.00002CrossRef Chien YH, Lee NC, Chiang SC, Desnick RJ, Hwu WL (2012) Fabry disease: incidence of the common later-onset α-galactosidase A IVS4+919G→A mutation in Taiwanese newborns—superiority of DNA-based to enzyme-based newborn screening for common mutations. Mol Med 18(1):780–784. https://​doi.​org/​10.​2119/​molmed.​2012.​00002CrossRef
10.
Zurück zum Zitat Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP, Fabry Registry (2008) Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 93(2):112–28. https://doi.org/10.1016/j.ymgme.2007.09.013CrossRef Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP, Fabry Registry (2008) Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 93(2):112–28. https://​doi.​org/​10.​1016/​j.​ymgme.​2007.​09.​013CrossRef
19.
Zurück zum Zitat Sawada J, Katayama T, Kano K, Asanome A, Takahashi K, Saito T, Chinda J, Nakagawa N, Sato N, Kimura T, Yahara O, Momosaki K, Nakamura K, Hasebe N (2015) A sporadic case of Fabry disease involving repeated fever, psychiatric symptoms, headache, and ischemic stroke in an adult Japanese woman. Intern Med 54(23):3069–3074. https://doi.org/10.2169/internalmedicine.54.4719CrossRef Sawada J, Katayama T, Kano K, Asanome A, Takahashi K, Saito T, Chinda J, Nakagawa N, Sato N, Kimura T, Yahara O, Momosaki K, Nakamura K, Hasebe N (2015) A sporadic case of Fabry disease involving repeated fever, psychiatric symptoms, headache, and ischemic stroke in an adult Japanese woman. Intern Med 54(23):3069–3074. https://​doi.​org/​10.​2169/​internalmedicine​.​54.​4719CrossRef
20.
Zurück zum Zitat Callegaro D, Kaimen-Maciel DR (2006) Fabry’s disease as a differential diagnosis of MS. Int MS J 13(1):27–30 Callegaro D, Kaimen-Maciel DR (2006) Fabry’s disease as a differential diagnosis of MS. Int MS J 13(1):27–30
22.
Zurück zum Zitat Perrot X, Nighoghossian N, Derex L, Hermier M, Guffon N, Boulliat J, Trouillas P (2002) Accidents ischémiques vertébrobasilaires et méningite aseptique compliquant une maladie de Fabry [Vertebro-basilar ischemic strokes and aseptic meningitis, late complications of Fabry’s disease]. Rev Neurol (Paris) 158(5 Pt 1):596–8 (French) Perrot X, Nighoghossian N, Derex L, Hermier M, Guffon N, Boulliat J, Trouillas P (2002) Accidents ischémiques vertébrobasilaires et méningite aseptique compliquant une maladie de Fabry [Vertebro-basilar ischemic strokes and aseptic meningitis, late complications of Fabry’s disease]. Rev Neurol (Paris) 158(5 Pt 1):596–8 (French)
26.
Zurück zum Zitat Eng CM, Fletcher J, Wilcox WR, Waldek S, Scott CR, Sillence DO, Breunig F, Charrow J, Germain DP, Nicholls K, Banikazemi M (2007) Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 30(2):184–192. https://doi.org/10.1007/s10545-007-0521-2CrossRef Eng CM, Fletcher J, Wilcox WR, Waldek S, Scott CR, Sillence DO, Breunig F, Charrow J, Germain DP, Nicholls K, Banikazemi M (2007) Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 30(2):184–192. https://​doi.​org/​10.​1007/​s10545-007-0521-2CrossRef
28.
Zurück zum Zitat Eng CM, Niehaus DJ, Enriquez AL, Burgert TS, Ludman MD, Desnick RJ (1994) Fabry disease: twenty-three mutations including sense and antisense CpG alterations and identification of a deletional hot-spot in the alpha-galactosidase A gene. Hum Mol Genet 3(10):1795–1799. https://doi.org/10.1093/hmg/3.10.1795CrossRef Eng CM, Niehaus DJ, Enriquez AL, Burgert TS, Ludman MD, Desnick RJ (1994) Fabry disease: twenty-three mutations including sense and antisense CpG alterations and identification of a deletional hot-spot in the alpha-galactosidase A gene. Hum Mol Genet 3(10):1795–1799. https://​doi.​org/​10.​1093/​hmg/​3.​10.​1795CrossRef
29.
Zurück zum Zitat DeGraba T, Azhar S, Dignat-George F, Brown E, Boutière B, Altarescu G, McCarron R, Schiffmann R (2000) Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol 47(2):229–33CrossRef DeGraba T, Azhar S, Dignat-George F, Brown E, Boutière B, Altarescu G, McCarron R, Schiffmann R (2000) Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol 47(2):229–33CrossRef
30.
Zurück zum Zitat Biancini GB, Vanzin CS, Rodrigues DB, Deon M, Ribas GS, Barschak AG, Manfredini V, Netto CBO, Jardim LB, Giugliani R, Vargas CR (2012) Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy. Biochim Biophys Acta (BBA) - Mol Basis Dis 1822(2):226–232. https://doi.org/10.1016/j.bbadis.2011.11.001CrossRef Biancini GB, Vanzin CS, Rodrigues DB, Deon M, Ribas GS, Barschak AG, Manfredini V, Netto CBO, Jardim LB, Giugliani R, Vargas CR (2012) Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy. Biochim Biophys Acta (BBA) - Mol Basis Dis 1822(2):226–232. https://​doi.​org/​10.​1016/​j.​bbadis.​2011.​11.​001CrossRef
32.
Zurück zum Zitat Zago AC, Simon DI, Wang Y, Sakuma M, Chen Z, Croce K, Ustinov V, Shi C, Martinez Filho EE (2008) The importance of the interaction between leukocyte integrin Mac-1 and platelet glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory response to vascular injury. Arq Bras Cardiol. 90(1):54–63. https://doi.org/10.1590/s0066-782x2008000100009 (English, Portuguese)CrossRef Zago AC, Simon DI, Wang Y, Sakuma M, Chen Z, Croce K, Ustinov V, Shi C, Martinez Filho EE (2008) The importance of the interaction between leukocyte integrin Mac-1 and platelet glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory response to vascular injury. Arq Bras Cardiol. 90(1):54–63. https://​doi.​org/​10.​1590/​s0066-782x200800010000​9 (English, Portuguese)CrossRef
39.
Zurück zum Zitat Banas MC, Banas B, Hudkins KL, Wietecha TA, Iyoda M, Bock E, Hauser P, Pippin JW, Shankland SJ, Smith KD, Stoelcker B, Liu G, Gröne HJ, Krämer BK, Alpers CE (2008) TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 19(4):704–13. https://doi.org/10.1681/ASN.2007040395CrossRef Banas MC, Banas B, Hudkins KL, Wietecha TA, Iyoda M, Bock E, Hauser P, Pippin JW, Shankland SJ, Smith KD, Stoelcker B, Liu G, Gröne HJ, Krämer BK, Alpers CE (2008) TLR4 links podocytes with the innate immune system to mediate glomerular injury. J Am Soc Nephrol 19(4):704–13. https://​doi.​org/​10.​1681/​ASN.​2007040395CrossRef
42.
Zurück zum Zitat Fledelius HC, Sandfeld L, Rasmussen ÅK, Madsen CV, Feldt-Rasmussen U (2015) Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement. Acta Ophthalmol 93(3):258–264. https://doi.org/10.1111/aos.12588CrossRef Fledelius HC, Sandfeld L, Rasmussen ÅK, Madsen CV, Feldt-Rasmussen U (2015) Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement. Acta Ophthalmol 93(3):258–264. https://​doi.​org/​10.​1111/​aos.​12588CrossRef
44.
Zurück zum Zitat Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S, Chiu CY (2019) Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. N Engl J Med 380(24):2327–2340. https://doi.org/10.1056/NEJMoa1803396CrossRef Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S, Chiu CY (2019) Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. N Engl J Med 380(24):2327–2340. https://​doi.​org/​10.​1056/​NEJMoa1803396CrossRef
Metadaten
Titel
Aseptic meningitis in Fabry disease due to a novel GLA variant: an expanded phenotype?
verfasst von
Paulo Ribeiro Nóbrega
João Lucas Araújo Morais
Alliane Milliane Ferreira
Alisson Dantas de Medeiros
Beatrice Araújo Duarte
Deborah Moreira Rangel
Fabrício Oliveira Lima
Anderson Rodrigues Brandão de Paiva
Luciana Paim-Marques
Fernando Kok
André Luiz Santos Pessoa
Pedro Braga-Neto
Fernanda Martins Maia Carvalho
Publikationsdatum
12.09.2022
Verlag
Springer International Publishing
Erschienen in
Neurological Sciences / Ausgabe 1/2023
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-022-06388-y

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