Differences in clinical condition and genotype at time of diagnosis of cystic fibrosis by newborn screening or by symptoms

A M M Vernooij-van Langen; F L G R Gerzon; J G Loeber; E Dompeling; J E Dankert-Roelse

doi:10.1016/j.ymgme.2014.07.012

Differences in clinical condition and genotype at time of diagnosis of cystic fibrosis by newborn screening or by symptoms

Mol Genet Metab. 2014 Sep-Oct;113(1-2):100-4. doi: 10.1016/j.ymgme.2014.07.012. Epub 2014 Jul 16.

Authors

A M M Vernooij-van Langen¹, F L G R Gerzon², J G Loeber³, E Dompeling⁴, J E Dankert-Roelse⁵

Affiliations

¹ Department of Paediatrics, Hospital St Jansdal, P.O. Box 138, 3840 BA Harderwijk, The Netherlands. Electronic address: amm.vernooij@gmail.com.
² Department of Paediatrics, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
³ Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
⁴ Department of Paediatric Pulmonology, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
⁵ Department of Paediatrics, Atrium Medical Centre, P.O. Box 4446, 6401 CX Heerlen, The Netherlands.

PMID: 25077434
DOI: 10.1016/j.ymgme.2014.07.012

Abstract

Background: Early diagnosis through newborn screening (NBS) and early treatment of cystic fibrosis (CF) do lead to better prognosis. In the Netherlands, the median age for a clinical diagnosis is six months, and after newborn screening this is 30 days. It is unknown if being diagnosed at the age of six months or before two months leads to a clinically relevant difference of the clinical condition at the time of diagnosis.

Aim: The aim of this study is to assess the differences in clinical parameters at diagnosis between children with CF identified by newborn screening (NBS) or by clinical diagnosis (CD) in the Netherlands.

Methods: From July 1st, 2007 to January 1st, 2012 all newly diagnosed CF patients were reported to the Dutch Paediatric Surveillance Unit (DPSU). All paediatricians received a questionnaire to collect data on mutations and clinical condition at diagnosis. Non-classical CF was excluded from the analysis on clinical condition.

Results: 204 new CF diagnoses were reported to the DPSU, 33 were reported twice and three had no CF after further testing. 127 questionnaires were returned (76%); 85 children were diagnosed because of clinical symptoms, 40 after NBS and two because of a positive family history. The median age at diagnosis was 34 weeks for a clinical diagnosis and 3 weeks after NBS. Non-classical CF was more prevalent in the NBS group (6 clinical, 14 NBS), mostly F508del/R117H7T (12). Compared to the NBS group, significantly more patients in the CD group showed failure to thrive, respiratory symptoms, and hospitalizations. 62% of the CD group showed abnormal signs at physical examination compared to 4% of the NBS group.

Conclusion: At the time of diagnosis infants detected after NBS are in a significantly better condition than after a clinical diagnosis. Growth retardation is already seen when after NBS the diagnosis is confirmed, but NBS leads to a diagnosis before respiratory symptoms have developed.

Keywords: Clinical condition; Cystic fibrosis; Genotype; Newborn screening; Symptoms.

MeSH terms

Cystic Fibrosis / diagnosis*
Cystic Fibrosis / epidemiology
Cystic Fibrosis / genetics*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Gene Frequency
Genotype*
Humans
Infant
Infant, Newborn
Mutation
Neonatal Screening* / methods
Phenotype
Prevalence
Registries

Substances

Cystic Fibrosis Transmembrane Conductance Regulator