Cystic fibrosis (CF) is an inherited disease caused by a recessive gene, meaning that an affected child inherits one mutated gene from each parent. It causes thick secretions to form in the lungs and digestive system. Intensive efforts are ongoing to develop a cure for a number of different mutations causing the disease. Until a cure is found for each type, early detection and treatment can significantly extend the life span of children with the disease.
A report published on November 16 online in the journal Pediatrics presented details regarding a successful CF detection program in California. The report notes that in 2004, the Centers for Disease Control and Prevention (CDC) determined that newborn screening for CF was justified to minimize the impact of nutritional deficiencies and poor growth (and possibly decrease lung disease) caused by CF through early detection and proper treatment. By 2010, newborn screening for CF had been instituted throughout the US.
From 200 through 2005, the California Department of Public Health Genetic Disease Screening Program (GDSP) established six requirements and goals. One of the challenge that California confronted was a poor understanding of common CF mutations within its large and heterogeneous population. After establishing a CF registry and researching the CF mutations and immunoreactive trypsinogen (IRT; an indicator of CF) levels in CF patients and control subjects from three main race/ethnic groups in California, GDSP developed a 3-step model (IRT–mutation panel–DNA sequencing) for CF NBS.
The objective of the report was to describe the methods used and the program performance results for the first five years of newborn screening for CF in California. From July 16, 2007 through June 30, 2012, a total of 2,573,293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values 62 ng/mL or more (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with two or more mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with one mutation were considered carriers and their parents offered telephone genetic counseling.
The authors of the report detected 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (average follow-up: 4.5 years). The sensitivity (ability to detect CF) of the screening was 92%, and the positive predictive value (prediction of CF) was 34%. CF prevalence was 1 in 6,899 births. A total of 303 CFTR mutations were identified, including 78 new variants. The average age at referral to a CF care center was 34 days (18 days for step 2 screening and 37 days for step 3 screening test–positive infants).
The authors concluded that the 3-step model had high detection and low false-positive levels among the diverse California population.