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.
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.
Authors: T Yoshitama; S Nakao; T Takenaka; H Teraguchi; T Sasaki; C Kodama; A Tanaka; A Kisanuki; C Tei Journal: Am J Cardiol Date: 2001-01-01 Impact factor: 2.778
Authors: Alberto Ortiz; Dominique P Germain; Robert J Desnick; Juan Politei; Michael Mauer; Alessandro Burlina; Christine Eng; Robert J Hopkin; Dawn Laney; Aleš Linhart; Stephen Waldek; Eric Wallace; Frank Weidemann; William R Wilcox Journal: Mol Genet Metab Date: 2018-02-28 Impact factor: 4.797
Authors: A C Vedder; A Strijland; M A vd Bergh Weerman; S Florquin; J M F G Aerts; C E M Hollak Journal: J Inherit Metab Dis Date: 2006-02 Impact factor: 4.982
Authors: William R Wilcox; João Paulo Oliveira; Robert J Hopkin; Alberto Ortiz; Maryam Banikazemi; Ulla Feldt-Rasmussen; Katherine Sims; Stephen Waldek; Gregory M Pastores; Philip Lee; Christine M Eng; Laszlo Marodi; Kevin E Stanford; Frank Breunig; Christoph Wanner; David G Warnock; Roberta M Lemay; Dominique P Germain Journal: Mol Genet Metab Date: 2007-11-26 Impact factor: 4.797