Screening for Cystic Fibrosis LAB

Cystic Fibrosis is a chronic disease that affects one child every 2500-3000 newborns. It is one of the most common hereditary diseases in our population and is caused by the alteration of a protein that regulates saline exchanges with the consequent production of very dense secretions and salt-rich sweat. In its classical form the most affected apparatuses are the respiratory and gastrointestinal systems with consequent repeated infections and poor growth.

Newborn screening allows cystic fibrosis to be diagnosed early, even before the onset of symptoms, and to prevent certain complications, guaranteeing a better clinical course of the disease from the earliest months of life thanks to targeted and timely therapies.

Neonatal cystic fibrosis screening is mandatory in all Italian regions and is performed in Campania on all newborns - more than 50,000 a year (DGRC 2283/2006).

At all birth points in the Campania Region, non-invasive peripheral blood from the heel of newborns is collected between the second and fourth days of life, collected on filter paper (Guthrie Spot).

The spots are sent to the Screening Center of the A.O.R.N. Santobono-Pausilipon for the determination of the immunoreactive trypsinogen (IRT) - present at high concentrations in the blood of newborns suffering from cystic fibrosis. If the IRT values exceed the cut-off (48 ng / mL) the newborn is called to perform a second IRT dose between the twentieth and thirtieth day of life. All the spots whose IRTs exceed the second cut-off (37 ng / mL) are sent to CEINGE for the molecular investigation.

A DNA level analysis is performed on the DNA extracted from the card stock to search for the 57 most common cystic fibrosis mutations in our region (about 87% Detection Rate). Newborns affected by classical cystic fibrosis (which have two causative mutations), are taken in charge by the Specialist Pediatrics of Federico II who will assist them up to the age of 18.

Carrier infants (who have only one causative mutation) can investigate the molecular investigation by submitting to II and III level analysis (approximately 94% Detection Rate). The II level analysis involves the total sequencing of the CFTR gene that encodes the protein altered in Cystic Fibrosis.

The III level analysis involves the search for the CFTR gene macro-selection causative of 1-3% of the cases of Cystic Fibrosis.

All newborns analyzed at the Ceinge, even if they were negative in the investigation, are referred to by the Specialist Pediatrics of the Federico II to carry out the sweat test (a clinical test that doses salt concentrations in sweat, the gold standard for the diagnosis of Cystic Fibrosis).

Parents of affected and / or carrier infants are given the opportunity to search for mutations found in children by identifying the healthy carrier of Cystic Fibrosis (via peripheral blood sample).

The awareness of carrier status is useful not only on a personal level, but also on a family level in the expectation of future pregnancies (two carriers have a 25% chance of procreating a child with Cystic Fibrosis).