Ivana Capuano1, Carlo Garofalo2, Pasquale Buonanno3, Michele Pinelli4, Teodolinda Di Risi5, Sandro Feriozzi6, Eleonora Riccio7, Antonio Pisani7. 1. Department of Public Health, Chair of Nephrology, University Federico II of Naples, Via Pansini 5, 80131, Naples, Italy. ivanacapuano@libero.it. 2. Nephrology Division, University of Naples-"Luigi Vanvitelli"-Medical School, Naples, Italy. 3. Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", via Pansini, 5, 80131, Naples, Italy. 4. Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei, 34, 80078, Pozzuoli, Italy. 5. Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Via Tommaso De Amicis, 95, 80131, Naples, Italy. 6. Centro di Riferimento di Nefrologia e Dialisi, Ospedale Belcolle, Viterbo, Italy. 7. Department of Public Health, Chair of Nephrology, University Federico II of Naples, Via Pansini 5, 80131, Naples, Italy.
Abstract
BACKGROUND: Fabry disease (FD) is a rare X-linked genetic disorder of glycosphingolipid catabolism caused by mutations in the GLA gene. Its heterogeneous presentation, the paucity of specific early markers, and the absence of a genotype-phenotype correlation are associated with a delayed or missed diagnosis. The true prevalence of FD remains so far unknown. METHODS: A systematic search of FD screening studies in dialysis patients published from January 1995 until January 2019 was performed to reanalyze the prevalence of GLA mutations in this population after assigning their correct phenotype. RESULTS: Twenty five screening studies involving 39,621 dialysis patients were included. Of them, 116 [91 males (0.23%) and 25 females (0.06%)] were positive to the GLA sequencing analysis. 56 (48.2%) had benign variant, 52 (44.8%) a pathogenic GLA mutation (39 classic and 13 late onset mutations) and 8 (6.9%) a mutation of uncertain significance. The overall prevalence of GLA variants was 0.24% [CI 95%, 0.17-0.32] while the overall prevalence recalculated on basis of only pathogenetic mutations was 0.14% [CI 95%, 0.08-0.20]. This difference was significant (P = 0.048). CONCLUSIONS: Although the real prevalence of classic FD is low, the screening in the high-risk renal population remains of primary interest as an early diagnosis is fundamental for a timely specific therapy; moreover, the identification of index cases could allow patients' relatives to be investigated and promptly treated.
BACKGROUND:Fabry disease (FD) is a rare X-linked genetic disorder of glycosphingolipid catabolism caused by mutations in the GLA gene. Its heterogeneous presentation, the paucity of specific early markers, and the absence of a genotype-phenotype correlation are associated with a delayed or missed diagnosis. The true prevalence of FD remains so far unknown. METHODS: A systematic search of FD screening studies in dialysis patients published from January 1995 until January 2019 was performed to reanalyze the prevalence of GLA mutations in this population after assigning their correct phenotype. RESULTS: Twenty five screening studies involving 39,621 dialysis patients were included. Of them, 116 [91 males (0.23%) and 25 females (0.06%)] were positive to the GLA sequencing analysis. 56 (48.2%) had benign variant, 52 (44.8%) a pathogenic GLA mutation (39 classic and 13 late onset mutations) and 8 (6.9%) a mutation of uncertain significance. The overall prevalence of GLA variants was 0.24% [CI 95%, 0.17-0.32] while the overall prevalence recalculated on basis of only pathogenetic mutations was 0.14% [CI 95%, 0.08-0.20]. This difference was significant (P = 0.048). CONCLUSIONS: Although the real prevalence of classic FD is low, the screening in the high-risk renal population remains of primary interest as an early diagnosis is fundamental for a timely specific therapy; moreover, the identification of index cases could allow patients' relatives to be investigated and promptly treated.
Authors: Teodolinda Di Risi; Roberta Vinciguerra; Mariella Cuomo; Rosa Della Monica; Eleonora Riccio; Sirio Cocozza; Massimo Imbriaco; Giovanni Duro; Antonio Pisani; Lorenzo Chiariotti Journal: Clin Epigenetics Date: 2021-02-02 Impact factor: 6.551