Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

Alice Castaldo; Chiara Cimbalo; Raimondo J Castaldo; Marcella D'Antonio; Manuela Scorza; Laura Salvadori; Angela Sepe; Valeria Raia; Antonella Tosco

doi:10.3390/diagnostics10080570

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

Diagnostics (Basel). 2020 Aug 8;10(8):570. doi: 10.3390/diagnostics10080570.

Authors

Alice Castaldo¹, Chiara Cimbalo¹, Raimondo J Castaldo¹, Marcella D'Antonio², Manuela Scorza², Laura Salvadori¹, Angela Sepe¹, Valeria Raia¹, Antonella Tosco¹

Affiliations

¹ Department of Translational Medical Sciences, Cystic Fibrosis Centre, University Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.
² CEINGE-Advanced Biotechnology, Via Gaetano Salvatore 486, 80145 Naples, Italy.

Abstract

Background: Newborn screening (NBS) early-identifies cystic fibrosis (CF), but in CF-screening positive inconclusive diagnosis (CF-SPID) the results of immunoreactive trypsinogen (IRT), molecular analysis and sweat test (ST) are discordant. A percentage of CF-SPID evolves to CF, but data on long-term monitoring are lacking. We describe the follow-up of all CF and CF-SPID identified between 2008 and 2019.

Methods: NBS was performed by IRT followed by molecular analysis and ST between 2008 and 2014; double IRT followed by molecular analysis and ST after 2014.

Results: NBS revealed 47 CF and 99 CF-SPID newborn, a ratio 1:2.1-the highest reported so far. This depends on the identification by gene sequencing of the second variant with undefined effect in 40 CF-SPID that otherwise would have been defined as carriers. Clinical complications and pulmonary infections occurred more frequently among CF patients than among CF-SPID. Two CF-SPID cases evolved to CF (at two years), while eight evolved to CFTR-related disorders (CFTR-RD), between one and eight years, with bronchiectasis (two), recurrent pneumonia (four, two with sinonasal complications), recurrent pancreatitis (two). No clinical, biochemical or imaging data predicted the evolution.

Conclusion: Gene sequencing within the NBS reveals a higher number of CF-SPID and we first describe an approach to early identify CFTR-RD, with relevant impact on their outcome.

Keywords: CF-SPID; CFTR-RD; cystic fibrosis; genotype–phenotype correlation; newborn screening.