Pancreatic phenotype in cystic fibrosis patients identified by mutation screening

Marco Cipolli ^1*, Carlo Castellani ¹, Bridget Wilcken ², John Massie ³, Karen McKay ³, Margie Gruca ⁴, Anna Tamanini ⁵, Maurice Baroukh Assael ⁵ and Kevin Gaskin ⁴

¹ Verona Cystic Fibrosis Centre, Italy
² New South Wales Newborn Screening Program, Royal Alexandra Hospital for Children, Westmead, Australia
³ Department of Respiratory Medicine, Royal Alexandra Hos, Australia
⁴ James Fairfax Institute of Paediatric Nutrition, University of Sydney, Australia
⁵ Verona, Cystic Fibrosis Centre, Italy

^* To whom correspondence should be addressed. E-mail: marco.cipolli{at}azosp.vr.it.

Accepted 15 April 2007

Abstract

Objective: To determine the pancreatic phenotype of infants with cystic fibrosis (CF) diagnosed in the first week of life by a combined immunoreactive trypsin/mutation screening program.

Design: A prospective evaluation of pancreatic function in CF infants at the time of neonatal diagnosis and up to the first 12 years of life.

Setting: Two different centres, Verona (VCFC), Italy and Westmead (CHW), Australia to enable comparison of results between a region where <60% of CF patients have ¡ a single DF508 mutation and another with ¡90% having ¡ one DF508 mutation.

Patients: A total of 315 CF children, 149 at VCFC and 166 at CHW.

Interventions: Fat balance studies over 3-5 days and pancreatic stimulation tests with main outcome measures being faecal fat or pancreatic colipase secretion.

Results: At VCFC 34 (23%) and at CHW 46 (28%) were pancreatic sufficient with normal absorption at diagnosis within the first month of life. Of those with two Class I, II or III ¡°severe¡± mutations 15% and with Class IV or V mutations 26/28 (93%) were PS at this early age. Of the total 80 with PS 18 have developed PI up to 5 years of age. All 18 had two ¡°severe¡± mutations.

Conclusion: Neonatal mutational screening programs for CF are less likely to detect PS patients with non-DF508 mutations. Of those PS patients who are detected, those with two severe Class I, II or III mutations are particularly at high risk of becoming PI during early childhood.

Keywords: cystic fibrosis, genetic analysis, neonatal screening, pancreatic phenotype

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