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Open Access 25-04-2023 | Stroke | Original Article

Late-onset fabry disease due to the p.Phe113Leu variant: the first italian cluster of five families

Authors: Vittoria Cianci, Angelo Pascarella, Lucia Manzo, Sara Gasparini, Oreste Marsico, Anna Mammì, Carmelo Massimiliano Rao, Claudio Franzutti, Umberto Aguglia, Edoardo Ferlazzo

Published in: Metabolic Brain Disease | Issue 6/2023

Abstract

Background

The GLA c.337T > C (p.Phe113Leu) is a known pathogenic variant associated to late-onset Fabry disease phenotype with predominant cardiac manifestations. A founder effect was demonstrated in a large cohort in the Portuguese region of Guimarães. Herein we report an in-depth phenotype description of a cluster of five Southern Italy families.

Methods

Family pedigrees of five index males with the p.Phe113Leu variant were obtained and all at-risk relatives underwent biochemical and genetical screening test. Carriers of GLA p.Phe113Leu variant underwent subsequent multidisciplinary clinical and instrumental evaluation.

Results

Thirty-one (16 M, 15 F) individuals with p.Phe113Leu pathogenic variant were identified. Sixteen out of 31 patients (51.6%) had cardiac manifestations. Notably, myocardial fibrosis was found in 7/8 patients, of whom 2 were under 40 years. Stroke occurred in 4 patients. White matter lesions were detected in 12/19 patients and occurred in 2/10 of subjects under 40 years. Seven females complained of acroparesthesias. Renal involvement occurred in 10 patients. Angiokeratomas were evident in 9 subjects. Eyes, ear, gastrointestinal and pulmonary involvement occurred in the minority of subjects.

Conclusion

This study demonstrates that a cluster of subjects with p.Phe113Leu pathogenic variant is also present in Southern Italy. Disease manifestations are frequent in both sexes and may occur early in life. Cardiac involvement represents the core manifestation, but neurological and renal involvement is also frequent, suggesting that extra-cardiac complications deserve clinical attention.

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http://www.dbfgp.org/dbFgp/fabry. Accessed 15 February 2023

http://www.fabrygenphen.com. Accessed 15 February 2023

Title: Late-onset fabry disease due to the p.Phe113Leu variant: the first italian cluster of five families
Authors: Vittoria Cianci
Angelo Pascarella
Lucia Manzo
Sara Gasparini
Oreste Marsico
Anna Mammì
Carmelo Massimiliano Rao
Claudio Franzutti
Umberto Aguglia
Edoardo Ferlazzo
Publication date: 25-04-2023
Publisher: Springer US
Keywords: Stroke
Fabry Disease
Published in: Metabolic Brain Disease / Issue 6/2023
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-023-01216-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Late-onset fabry disease due to the p.Phe113Leu variant: the first italian cluster of five families

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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