@article {Dohenyjmedgenet-2017-105080, author = {Dana Doheny and Ram Srinivasan and Silvere Pagant and Brenden Chen and Makiko Yasuda and Robert J Desnick}, title = {Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995{\textendash}2017}, elocation-id = {jmedgenet-2017-105080}, year = {2018}, doi = {10.1136/jmedgenet-2017-105080}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Fabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A (GLA) mutations, results in two major subtypes, the early-onset Type 1 {\textquoteleft}Classic{\textquoteright} and the Type 2 {\textquoteleft}Later-Onset{\textquoteright} phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised {\textquoteleft}benign/likely-benign{\textquoteright} variants, thereby inflating prevalence estimates.Methods Online databases were searched for all FD screening studies in high-risk clinics (1995{\textendash}2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined.Results Of 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9\% of males and 74.1\% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21\% males and 0.15\% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25\% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94\% males and 0.90\% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13\% males and 0.14\% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60\%), except more male cardiac patients (75\%) had type 2 Later-Onset phenotype.Conclusions Compared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13\% of stroke to ~0.9\% of cardiac male or female screenees.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/early/2018/01/12/jmedgenet-2017-105080}, eprint = {https://jmg.bmj.com/content/early/2018/01/12/jmedgenet-2017-105080.full.pdf}, journal = {Journal of Medical Genetics} }