Inconclusive Diagnosis after Newborn Screening for Cystic Fibrosis
Abstract
:1. Introduction
2. Inconclusive Diagnosis after Newborn Screening
2.1. Definition of CRMS/CFSPID
2.2. Incidence of CRMS/CFSPID across Europe
2.3. Assessment of CFTR Protein Function
3. Monitoring Infants Designated CRMS/CFSPID
3.1. Outcomes and Conversion to a Final Diagnosis of CF in Infants Designated CRMS/CFSPID
3.2. Management of Infants with CRMS/CFSPID Designation
4. CRMS/CFSPID Registry Database
Funding
Acknowledgments
Conflicts of Interest
References
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Positive NBS | And | Or | |
---|---|---|---|
CRMS [5] US | Asymptomatic infants with hypertrypsinemia at birth | Persistently intermediate sweat chloride levels 1 and fewer than 2 CF-causing CFTR mutations | Sweat chloride concentration <30 mmol/L and 2 CFTR mutations with 0 or 1 known to be CF-causing |
CFSPID [6] Europe | Asymptomatic infants with hypertrypsinemia at birth | 0 or 1 CFTR mutation, plus intermediate sweat chloride (30–59 mmol/L) | 2 CFTR mutations, at least 1 of which has unclear phenotypic consequences, plus a normal sweat chloride (<30 mmol/L) |
CRMS/CFSPID [8] | Infants with positive newborn screening test | Sweat chloride <30 mmol/L and 2 CFTR mutations with 0 or 1 CF-causing CFTR mutation | Sweat chloride 30–59 mmol/L and 0 or 1 CF-causing CFTR mutation |
Kharrazi et al. [14] | Groves et al. [15] | Ren et al. [16] | Levy et al. [17] | Terlizzi et al. [18] | Ooi et al. [19] | Munck et al. [21] | |
---|---|---|---|---|---|---|---|
Study design | Retrospective | Retrospective case control | CFF registry | Cross sectional | Retrospective | Prospective case control | Prospective case control |
Country | USA California | Australia | US | US Wisconsin | Italy Tuscany | Canada, Italy | France |
Birth period | 2007–2012 | 1996–2010 | 2010–2012 | 1994–2012 | 2011–2016 | 2007–2013 | 2002–2009 |
Follow up duration (y) | Mean 4.5 | 10 | 1 | 8 | Median 0.6 | Median 2.2 | Mean 7.4 |
Number CF | 345 | 225 | 1540 | 300 | 32 | 80 | 63 |
Number CRMS/CFSPID | 533 | 29 2 | 309 | 57 | 50 | 82 | 63 2 |
CF:CRMS/CFSPID | 0.65:1 | 7.8:1 | 5:1 | 5.2:1 | 0.64:1 | 1.8:1 6 | 6.3:1 6 |
Conversion to CF, N (%) | 20 (5.8) | 14/29 (48) matched to CF | NA 4 | NA 4 | 5 (10) | 9 (11) | 28(44) |
Increased SCC ≥60 mmol/L | 17 | 2 3 | 5 | 2 | 8 | ||
2 CF causing mutations | 0 | 0 | 0 | 4 | 12 | ||
Both criteria | 0 | 0 | 0 | 3 | 8 | ||
Other criteria | 3 | 12 | 0 | 0 | 0 | ||
Age at conversion (y) | Mean 2.5 ± 1.4 | Median 2 (0.2–4) | Mean 1.8 ± 1.2 | Unk 1 | |||
Pseudomonas aeruginosa, N (%) | Unk 1 | 78.6 | 10.7 | 39 | 25 5 | 12 | 24 |
Pancreatic insufficiency, N (%) | 3/15 (15) | 4/29 (14) | 14/309 (4.5) | 0 | 0 | 0 | 0 |
F508del/R117H, N (%) | Unk 1 | 4/14 (29) | 80/309 (26) | 37/57 (63) | 0 | 16/82 (19.5) | 27/63 (43) |
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Munck, A. Inconclusive Diagnosis after Newborn Screening for Cystic Fibrosis. Int. J. Neonatal Screen. 2020, 6, 19. https://doi.org/10.3390/ijns6010019
Munck A. Inconclusive Diagnosis after Newborn Screening for Cystic Fibrosis. International Journal of Neonatal Screening. 2020; 6(1):19. https://doi.org/10.3390/ijns6010019
Chicago/Turabian StyleMunck, Anne. 2020. "Inconclusive Diagnosis after Newborn Screening for Cystic Fibrosis" International Journal of Neonatal Screening 6, no. 1: 19. https://doi.org/10.3390/ijns6010019
APA StyleMunck, A. (2020). Inconclusive Diagnosis after Newborn Screening for Cystic Fibrosis. International Journal of Neonatal Screening, 6(1), 19. https://doi.org/10.3390/ijns6010019