Immunoreactive trypsinogen

Measurement of immunoreactive trypsinogen (IRT) in blood of newborn babies is an assay in rapidly increasing use as a screening test for cystic fibrosis (CF).[1]

In CF, there is poor release from pancreatic ducts. Trypsinogen is a pancreatic enzyme precursor found in the blood that is raised in most of those with CF at birth, regardless of whether their mutation is pancreatic sufficient or insufficient. The concentration of IRT is elevated in babies with CF since pancreatic ducts are partially blocked leading to abnormal enzyme drainage. This occurs even if infants are pancreatic sufficient. Heterozygous carriers of cystic fibrosis can cause a raised IRT and it is therefore not diagnostic in isolation.[2]

IRT is measured in routine heel-prick blood taken for biochemical screening of all newborn infants born in the UK. This test is one of a number of completed in newborn screening (the "Guthrie Test"). In Australia it is known 94% of those with eventual diagnosis of CF have a positive IRT on newborn screen. Samples with a raised IRT (defined as highest 1% of values) are then screened for common CF gene mutations. Each centre has a slightly different gene panel, currently 40-50 of the most common genes are sequenced, however there are more than 2000 known mutations so gene panel testing does miss occasional CF patients.

If gene testing finds one mutation they will then have a sweat test to help confirm the diagnosis. Sweat testing is more likely to be equivocal in infants and typically not attempted in those under 5kg. If sweat test is positive more expansive gene testing is considered. If two mutations are found they are diagnosed with CF.