Table 3.
The most important FD pilot studies and screening programs worldwide.
| Study Period | Country | Method | Type of Cutoff | Number of NBS Samples | Number of below Cutoff Samples | Number of below Cutoff Samples/100,000 Newborns | Confirmed Patients from Genetic Analysis * | Presumed Incidence ** | Source of Data |
|---|---|---|---|---|---|---|---|---|---|
| Europe | |||||||||
| 2003–2005 | Italy | Fluorometric enzyme assay | fixed | 37,104 (only males) | 12 (m) | 32 (m) | 12 (m) | 1:3100 (m) | Spada et al. [22] |
| 2008 | Spain | Fluorometric enzyme assay | fixed | 14,600 (m 7575) | 106 (m 68) | 726 (m 898) | 37 (m 20) | 1:394 (m 1:378) | Colon et al. [52] |
| 2010–2012 | Italy | Fluorometric enzyme assay | fixed | 3403 (m 1702) | 0 | 0 | 0 | / | Paciotti et al. [53] |
| 2010 ** | Austria | MS/MS | fixed | 34,736 (deidentified) | 28 | 81 | 9 (m 6) | 1:3860 | Mechtler et al. [54] |
| 2011 *** | Hungary | MS/MS | fixed | 40,024 (deidentified) | 34 | 85 | 3 | 1:13,341 | Wittmann et al. [55] |
| 2015–2021 | Italy | MS/MS | fixed | 173,342 (m 89,485) | 23 (m 22) | 13 (m 25) | 22 (m) | 1:7879 (m 1:4068) | Gragnaniello et al. [45] |
| Asia | |||||||||
| 2006–2008 | Taiwan | Fluorometric enzyme assay | fixed | 171,977 (m 90,288) | 94 (m 91) | 55 (m 53) | 75 (m 73) | 1:2293 (m 1:1237) | Hwu et al. [23] |
| 2006–2018 | Japan | Fluorometric enzyme assay | fixed | 599,711 | 138 | 23 | 108 (m 64) | 1:5552 | Sawada et al. [56] |
| 2007–2010 | Japan | Fluorometric enzyme assay | fixed | 21,170 (m 10,827) | 7 (m 5) | 33 (m 46) | 6 (5 m) | 1:3024 (m 1:2166) | Inoue et al. [57] |
| 2007–2014 | Japan | Fluorometric enzyme assay | fixed | 2443 | 2 (m 2) | 82 | 2 (m 2) | 1:1222 | Chinen et al. [58] |
| 2008–2014 | Taiwan | Fluorometric enzyme assay then MS/MS | fixed | 792,247 (m 412,299) | 764 (m 425) | 96 (m 103) | 324 (m 272) | 1:2445 (m 1:1515) | Liao et al. [59] |
| 2010–2013 | Taiwan | MS/MS (compared with fluorometry) | fixed | 191,767 | 79 | 41 | 64 (m 61) | 1:2996 | Liao et al. [41] |
| 2015–2019 | Taiwan | MS/MS | fixed | 137,891 | 13 | 19 | 13 | 1:10,607 | Chiang et al. [60], Chien et al. [46] |
| 2019–2022 | China | MS/MS | %DMA | 38,945 | 21 | 54 | 3 | 1:12,982 | Li et al. [61] |
| USA | |||||||||
| 2011–2013 *** | California | MS/MS, immunocapture assay, DMF (comparative) | 89,508 (m 44,664) (deidentified) | Variable based on method | Not applicable | 50 (m 46) | 1:1790 (m 1:1970) | Sanders et al. [34] | |
| 2013 ** | Washington State | MS/MS | %DMA | 108,905 (m 54,800) (deidentified) | 16 (m 13) | 15 (m 24) | 7 (m 7) | 1:15,558 (m 1:7800) | Scott et al. [62] |
| 2013 | Missouri | DMF | fixed | 43,701 | 28 | 64 | 15 (m 15) | 1:2913 | Hopkins et al. [14] |
| 2013–2019 | New York | MS/MS | % DMA | 65,605 | 31 | 47 | 7 (m 7) | 1:9372 | Wasserstein et al. [63] |
| 2014–2016 | Illinois | MS/MS | % DMA | 219,793 | 107 | 49 | 32 (m 32) | 1:6968 | Burton et al. [64] |
| 2016 *** | Washington State | MS/MS | % DMA | 43,000 (deidentified) | 8 | 19 | 6 | 1:7167 | Elliot et al. [38] |
| Latin America | |||||||||
| 2012–2016 | Petroleos Mexicanos Health Services | MS/MS | fixed | 20,018 (m 10,241) | 5 (m 5) | 25 (m 49) | 5 (m 5) | 1:4003 (m 1:2048) | Navarrete-Martinez et al. [65] |
| 2017 | Brazil | DMF | fixed | 10,527 | 0 | 0 | 0 | / | Camargo Neto et al. [66] |
* We include all patients carrying a GLA variant. ** Disease incidence is only an estimate, assuming that all genetically confirmed newborns will develop symptoms. *** Because most pilot NBS are anonymous, confirmatory tests could not be performed. In these studies, samples that screen positive biochemically are genotyped. Abbreviations: m: males; DMA: daily mean activity; DMF: digital microfluidics; MS/MS: tandem mass spectrometry.