Table 5.
Newborn screening studies for Pompe disease.
| Country | Newborns screened | Screening Method/Criteria | Outcome | Ref. |
|---|---|---|---|---|
| USA-Washington | 111,544 | MS/MS; cutoff of < 2.60 mmol/h/L (<15% of mean) | 4 PD cases (1/27, 800), 3 carriers with an additional pseudodeficiency allele, 6 were heterozygotes for a pseudodeficiency allele only; PPV 0.24; FPR 1/8600 | 86 |
| 5055 | MS/MS; cutoff: < 20% daily mean activity | 5 with low GAA activity | 87 | |
| USA-Missouri | 27,724 | digital microfluidics | 3 PD cases (1/8,657): 1 classic, 1 non-classic IOPD & 1 LOPD; 3 false positive results (carrier status unknown), 1 pseudodeficiency, 2 carriers, 2 pending cases | 88 |
| USA-Illinois | 8,012 | digital microfluidics | 2 false positive | 89 |
| Taiwan | 344,056 (2005-2009) | fluorescence assay, NAG/GAA > 60 & GAA inhibition by acarbose > 80%, 2nd tier: lymphocyte GAA activity < 5% of normal mean & GAA activity in skin fibroblasts, GAA sequencing | 13 LOPD (1/26,466) & 6 IOPD cases | 90 |
| 473,738 (2005-2011) | fluorescence assay, NAG/GAA ratio ≥ 100 | 9 IOPD & 19 LOPD cases; NAG/GAA cutoff ratio≥ 60 (PPV) of 63.4% | 91 | |
| Japan | 496 healthy controls, 29 PD cases & 5 PD carriers (530 DBS) | GAA activity < 8% of normal mean & % GAA inhibition > 60% and NAG/GAA ratio > 30 | 5 healthy pseudodeficiency homozygots & 1 obligate carrier | 92 |
| Italy | 3403 | Fluorescent GAA activity; cutoff: < 35% of average control activities | 3 cases with low GAA activity (final status not confirmed) | 93 |
| Hungary | 40,024 | MS/MS followed by molecular confirmation | 9 PD cases | 94 |
| Germany | 3251 | MS/MS & fluorimetric assays; repeat testing in < 0.5% of DBS samples | No PD cases | 95 |
| 944 (symptomatic individuals) | 14 PD cases and 8 GAA carriers | |||
| Colombia | 4700 (DBS samples from symptomatic, high risk individuals; 3 months – 73 years old)) | Fluorometric microfluidic, molecular GAA analysis (some) | 16 PD cases | 96 |
| Austria | 34,736 (January - July, 2010) | ESI-MS/MS | 4 confirmed by GAA mutation analysis (1/8684). Most GAA missense mutations were LOPD; PPV 80%; 1 false positive case (FPR 30 per million) | 97 |
Abbreviations: acid glucosidase (GAA), false positive rate (FPR), infantile onset Pompe disease (IOPD), late onset Pompe disease (LOPD), MS/MS tandem mass spectrometry, neutral alpha-glucosidase (NAG), Pompe disease (PD), positive predictive value (PPV).