Tuttolomondo Antonino, Simonetta Irene, Duro Giovanni, Pecoraro Rosaria, Miceli Salvatore, Colomba Paolo, Zizzo Carmela, Nucera Antonia, Daidone Mario, Di Chiara Tiziana, Scaglione Rosario, Della Corte Vittoriano, Corpora Francesca, Vogiatzis Danai, Pinto Antonio
U.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.
CNR-IBIM: Institute of Biomedicine and Molecular Immunology "A. Monroy" Palermo, Palermo, Italy.
Oncotarget. 2017 May 29;8(37):61415-61424. doi: 10.18632/oncotarget.18250. eCollection 2017 Sep 22.
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.
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.
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.
安德森 - 法布里病（AFD）是一种先天性溶酶体酶病，由溶酶体外切半乳糖水解酶α - 半乳糖苷酶A的活性缺乏或缺失引起。这种缺陷导致糖鞘脂代谢改变，进而使其在溶酶体中积累，从而导致细胞和血管功能障碍。迄今为止，已报道了GLA基因内含子和外显子中的众多突变（根据最新数据超过1000种突变）。传统上，受影响的半合子男性的临床表现比女性更严重。然而，最近的研究描述了女性中严重的器官功能障碍。
本研究报告了三个西西里家族成员的临床、生化和分子学发现。这些患者的临床病史突出了法布里病在家族间和家族内显著的表型变异性，这与靶器官和临床表现的严重程度有关。
我们的发现与先前的数据一致，表明该疾病的基因型与表型相关性较小，这表明安德森 - 法布里病广泛的表型变异性并非完全归因于不同的基因突变，其他因素和机制似乎也参与了该疾病的发病机制和临床表达。此外，本研究强调了对每个先证者家族进行系谱分析以识别其他可能受影响亲属的重要性。
