Vito Terlizzi1, Laura Claut2, Antonella Tosco3, Carla Colombo2, Valeria Raia3, Benedetta Fabrizzi4, Marco Lucarelli5, Antonio Angeloni6, Giuseppe Cimino7, Alice Castaldo3, Laura Marsiglio8, Silviana Timpano8, Natalia Cirilli4, Laura Moroni2, Filippo Festini9, Pietro Piccinini10, Lucia Zavataro11, Paolo Bonomi12, Giovanni Taccetti11, Kevin W Southern13, Rita Padoan8. 1. Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children's University, Florence, Italy. Electronic address: vito.terlizzi@meyer.it. 2. Cystic Fibrosis Regional Reference Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy. 3. Paediatric Unit, Department of Translational Medical Sciences, Cystic Fibrosis Regional Reference Center, University of Naples Federico II, Naples, Italy. 4. Cystic Fibrosis Regional Reference Center, Mother - Child Department, United Hospitals, Ancona, Italy. 5. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; Pasteur Institute Cenci Bolognetti Foundation, Rome, Italy. 6. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. 7. Cystic Fibrosis Regional Reference Center, A.O.U. Policlinico Umberto I, Rome, Italy. 8. Cystic Fibrosis Regional Support Center, Department of Pediatrics, University of Brescia, ASST Spedali Civili Brescia, Brescia, Italy. 9. Department of Health Sciences, University of Florence, Florence, Italy. 10. Freelance Statistician, Bergamo, Italy. 11. Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children's University, Florence, Italy. 12. Freelance Statistician, Milan, Italy. 13. Department of Women's and Children's Health, University of Liverpool, Institute in the Park, Alder Hey Children's Hospital, Liverpool, United Kingdom.
Abstract
OBJECTIVE: We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres. METHODS: All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected. RESULTS: We enrolled 257 CF patientsand 336 infants with a CRMS/CFSPID designation (CF: CRMS/CFSPID ratio of 1:1.30).Blood immuno-reactive trypsinogen (IRT) was significantly lower in CRMS/CFSPID infants and the F508del variant accounted for only 20% of alleles. Children with CRMS/CFSPID showed a milder clinical course, pancreatic sufficiency compared to CF infants. Varied practice across centres was identified regarding sweat testing, chest radiograph (8-100%) and salt supplementation (11-90%). Eighteen (5.3%) CRMS/CFSPID infants converted or were reclassified to diagnosis of CF. Four infants (1.3%) developed a clinical feature consistent with a CFTR-related disorder (1.2%). Twenty-seven were re-classified as healthy carriers (8.0%) and 16 as healthy infants (4.8%). CONCLUSIONS: We have identified considerable variability in the evaluation and management of infants with an inconclusive diagnosis following NBS across six Italian centres. CRMS/CFSPID is more regularly seen in this population compared to countries with higher prevalence of F508del.Conversion to a CF diagnosis was recorded in 18 (5.3%) of CRMS/CFSPID infants and in 16 was as a result of increasing sweat chloride concentration.
OBJECTIVE: We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres. METHODS: All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected. RESULTS: We enrolled 257 CF patientsand 336 infants with a CRMS/CFSPID designation (CF: CRMS/CFSPID ratio of 1:1.30).Blood immuno-reactive trypsinogen (IRT) was significantly lower in CRMS/CFSPID infants and the F508del variant accounted for only 20% of alleles. Children with CRMS/CFSPID showed a milder clinical course, pancreatic sufficiency compared to CF infants. Varied practice across centres was identified regarding sweat testing, chest radiograph (8-100%) and salt supplementation (11-90%). Eighteen (5.3%) CRMS/CFSPID infants converted or were reclassified to diagnosis of CF. Four infants (1.3%) developed a clinical feature consistent with a CFTR-related disorder (1.2%). Twenty-seven were re-classified as healthy carriers (8.0%) and 16 as healthy infants (4.8%). CONCLUSIONS: We have identified considerable variability in the evaluation and management of infants with an inconclusive diagnosis following NBS across six Italian centres. CRMS/CFSPID is more regularly seen in this population compared to countries with higher prevalence of F508del.Conversion to a CF diagnosis was recorded in 18 (5.3%) of CRMS/CFSPID infants and in 16 was as a result of increasing sweat chloride concentration.
Authors: Joice de Faria Poloni; Thaiane Rispoli; Maria Lucia Rossetti; Cristiano Trindade; José Eduardo Vargas Journal: Biomed Res Int Date: 2021-12-02 Impact factor: 3.411