Pancreatic Function in Infants Identified as Having Cystic Fibrosis in a Neonatal Screening Program

Abstract

The use of the dried-blood immunoreactive-trypsin assay for the detection of cystic fibrosis in newborns has been questioned on the grounds that it may fail to identify patients with enough pancreatic function to have normal fat absorption. To investigate this possibility, we assessed pancreatic function in 78 patients identified in a neonatal screening program as having cystic fibrosis. The diagnosis of cystic fibrosis was confirmed by abnormal results on a sweat chloride test. The results of measurements of fecal fat excretion, pancreatic-stimulation tests, and estimations of the serum level of pancreatic isoamylase indicated that 29 of the 78 children (37 percent) had substantial preservation of pancreatic function. These children (median age, four years) had growth that was close to normal and comparable to growth in children with severe pancreatic insufficiency who received oral enzyme therapy. Pancreatic insufficiency subsequently developed in 6 of the 29 patients, at 3 to 36 months of age. We conclude that the serum immunoreactive-trypsin assay used in neonatal screening programs identifies patients with cystic fibrosis who have sufficient pancreatic function to have normal fat absorption and that a substantial proportion of infants identified as having cystic fibrosis are in this category.

Pancreatitis in Cystic Fibrosis and CFTR-Related Disorder

“…A small proportion (2-3%) of patients carrying severe mutations on both alleles are pancreatic sufficient (PS) at diagnosis, but most experience gradual transition from PS to PI (Waters et al,1990;Wilschanski & Durie, 2007). It is well established that PS-CF patients, who are often diagnosed at an older age, with more subtle disease manifestations, have mean sweat chloride values that are significantly lower than the current diagnostic reference criteria of 60 mmol/L (Farrell et al, 2008;Gilljam et al, 2004).…”

“…This is almost certainly due to the fact that some infants carrying severe mutations on both alleles have some residual exocrine pancreatic function at birth. However, almost all of the patients who are homozygous or compound heterozygous for severe mutations will develop PI within the first two years of life (Waters et al, 1990 Usually PS…”

“…The susceptibility of the pancreas to intraductal obstruction resulting from CFTR dysfunction is thought to be due to the high macromolecule concentration of the secretions and the dependence on the CFTR chloride (and bicarbonate) channel for maintaing fluid balance. Progressive ductal obstruction and fibrosis of acinar tissue presents as pancreatic insufficiency either at birth or in early childhood (Waters et al 1990). Complete pancreatic exocrine deficiency is the seen in 85% to 90% of patients with CF (Durno et al, 2002;Ooi et al, 2011a).…”

Monoclonal versus Polyclonal ELISA for Assessment of Fecal Elastase Concentration: Pitfalls of a New Assay

“…With regard to this point, the widely different results obtained with the well-established mET compared with the relatively new pET ELISA among our patients with CF are a disappointing finding. We can proceed from the assumption that the CF patients studied suffered from severely compromised exocrine pancreatic insufficiency because the disease inevitably leads to the destruction of virtually all pancreatic tissue: ϳ60% of neonates diagnosed with CF already suffer from pancreatic insufficiency (10 ). This proportion increases to 92% during the first year of life (11 ).…”

The effect of cystic fibrosis transmembrane conductance regulator on the function of acid/base transporters of human pancreatic duct cells

“…Moreover, as 62% of CF patients are born with a non-functional pancreas (Waters et al, 1990), gene therapy would need to be initiated in utero in the majority of cases. Thus, the smaller group of patients who are pancreatic sufficient at birth, but who become pancreatic insufficient in later life, might be best helped by gene therapy.…”