Late-onset fabry disease due to the p.Phe113Leu variant: the first italian cluster of five families
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Published:2023-04-25
Issue:6
Volume:38
Page:1905-1912
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ISSN:0885-7490
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Container-title:Metabolic Brain Disease
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language:en
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Short-container-title:Metab Brain Dis
Author:
Cianci VittoriaORCID, Pascarella AngeloORCID, Manzo LuciaORCID, Gasparini SaraORCID, Marsico OresteORCID, Mammì Anna, Rao Carmelo Massimiliano, Franzutti Claudio, Aguglia UmbertoORCID, Ferlazzo EdoardoORCID
Abstract
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.
Funder
Università degli studi “Magna Graecia” di Catanzaro
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology (clinical),Biochemistry
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