TY - JOUR

T1 - Systematic cascade screening in the Danish Fabry Disease Centre

T2 - 20 years of a national single-centre experience

AU - Effraimidis, Grigoris

AU - Rasmussen, Åse Krogh

AU - Dunoe, Morten

AU - Hasholt, Lis F.

AU - Wibrand, Flemming

AU - Sorensen, Soren S.

AU - Lund, Allan M.

AU - Kober, Lars

AU - Bundgaard, Henning

AU - Yazdanfard, Puriya D.W.

AU - Oturai, Peter

AU - Larsen, Vibeke A.

AU - de Abreu, Vitor Hugo Fraga

AU - Enevoldsen, Lotte Hahn

AU - Kristensen, Tatiana

AU - Svenstrup, Kirsten

AU - Bille, Margrethe Bastholm

AU - Arif, Farah

AU - Mogensen, Mette

AU - Klokker, Mads

AU - Backer, Vibeke

AU - Kistorp, Caroline

AU - Feldt-Rasmussen, Ulla

N1 - Publisher Copyright: Copyright: © 2022 Effraimidis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022

Y1 - 2022

N2 - The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years’ (2001–2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.

AB - The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years’ (2001–2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.

U2 - 10.1371/journal.pone.0277767

DO - 10.1371/journal.pone.0277767

M3 - Journal article

C2 - 36383556

AN - SCOPUS:85142175896

VL - 17

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

M1 - e0277767

ER -