Dataset Information

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

ABSTRACT:

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.

SUBMITTER: Tuttolomondo A

PROVIDER: S-EPMC5617434 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

Tuttolomondo Antonino A Simonetta Irene I Duro Giovanni G Pecoraro Rosaria R Miceli Salvatore S Colomba Paolo P Zizzo Carmela C Nucera Antonia A Daidone Mario M Di Chiara Tiziana T Scaglione Rosario R Della Corte Vittoriano V Corpora Francesca F Vogiatzis Danai D Pinto Antonio A

Oncotarget 20170529 37

<h4>Background</h4>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. Traditi ...[more]

PMID: 28977874

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Project description:BackgroundTo date, only limited data are available on right atrium (RA) morphofunctional remodeling in Fabry disease (FD).PurposeWe aimed to investigate RA structural and functional remodeling in patients with FD vs. healthy controls using 2D speckle tracking echocardiography (STE) and to explore whether any differences exist in FD patients with and without left ventricular hypertrophy (LVH).MethodsWe prospectively enrolled patients with FD and controls matched for age, sex, and cardiovascular risk factors. Patients with FD were divided in two groups according to the presence/absence of LVH (LVH+: left ventricular wall thickness >12 mm). All patients underwent standard echocardiography and STE analysis investigating the mechanics of all cardiac chambers, including RA reservoir, contractile and conduit strain.ResultsA total of 64 patients with FD (50% males; mean age 50 ± 17 years; 51.5% LVH+) and 64 control patients were included in the study. Focusing on right chambers, RA and right ventricular (RV) dimensions were similar between FD and controls. No differences were found for tricuspid annular plane systolic excursion (p = 0.073) and RV fractional area change (p = 0.461), while RV systolic Tissue Doppler velocity was reduced in patients with FD (p = 0.041). STE analysis revealed impaired strain values for all cardiac chambers in FD vs controls, specifically: left ventricular global longitudinal strain (LV-GLS, p < 0.001), left atrial (LA) reservoir strain (p = 0.001), conduit strain (p = 0.012), and contractile strain (p < 0.001), RV-GLS and RV free wall strain (p < 0.001). Similarly, all RA strain phases were significantly reduced in patients with FD compared with control patients (RA reservoir 27.4 ± 11.1 vs. 41.9 ± 8.3%, p < 0.001; RA contractile 9.9 ± 5.1 vs. 18.0 ± 4.9%, p < 0.001; RA conduit 19.1 ± 8.1 vs. 24.1 ± 8.1%, p = 0.001). When comparing FD patients without LVH to controls, it was found that RA reservoir and contractile strains were significantly reduced in the former (p < 0.001). In multivariable linear regression analyses, LA reservoir strain (p = 0.010) and LV-GLS (p = 0.044) emerged as independent correlates of RA mechanics after adjustments were made for RA dimensions, RV systolic function parameters and hypertrophy, and LV maximal wall thickness.ConclusionsIn FD impaired RA strain is a common finding. RA reservoir and contractile strains are reduced in FD patients even before LVH ensues, as compared to controls. LA reservoir strain and LV-GLS show an independent correlation with RA reservoir strain.

Dataset Information

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

Background

The aim of the study

Discussion

Publications

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

Similar Datasets

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