Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease
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Antonino Tuttolomondo1, Irene Simonetta1, Giovanni Duro2, Rosaria Pecoraro1, Salvatore Miceli1, Paolo Colomba2, Carmela Zizzo2, Antonia Nucera3,4, Mario Daidone1, Tiziana Di Chiara1, Rosario Scaglione1, Vittoriano Della Corte1, Francesca Corpora1, Danai Vogiatzis1 and Antonio Pinto1
1U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), University of Palermo, Palermo, Italy
2CNR-IBIM: Institute of Biomedicine and Molecular Immunology “A. Monroy” Palermo, Palermo, Italy
3Stroke Unit, Neurology, Saint Andrea Hospital, La Spezia, Italy
4Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada
Antonino Tuttolomondo, email: [email protected]
Keywords: Anderson-Fabry disease (AFD), family, variability
Received: March 20, 2017 Accepted: April 11, 2017 Published: May 29, 2017
Background: Anderson-Fabry disease (AFD) is an inborn lysosomal enzymopathy resulting from the deficient or absent activity of the lysosomal exogalactohydrolase, α-galactosidase A. This deficiency, results in the altered metabolism of glycosphingolipids which leads to their accumulation in lysosomes, thus to cellular and vascular dysfunction. To date, numerous mutations (according to recent data more than 1000 mutations) have been reported in the GLA intronic and exonic mutations. Traditionally, clinical manifestations are more severe in affected hemizygous males than in females. Nevertheless, recent studies have described severe organ dysfunction in women.
The aim of the study: This study reports clinical, biochemical, and molecular findings of the members of three Sicilian families. The clinical history of these patients highlights a remarkable interfamilial and intrafamilial phenotypic variability which characterizes Fabry disease relative to target organs and severity of clinical manifestations.
Discussion: Our findings, in agreement with previous data, report a little genotype-phenotype correlation for the disease, suggesting that the wide phenotypic variability of Anderson-Fabry disease is not completely ascribable to different gene mutations but other factors and mechanisms seem to be involved in the pathogenesis and clinical expression of the disease. Moreover, this study emphasies the importance of pedigree analysis in the family of each proband for identifying other possibly affected relatives.
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