Historical Background

The clinical and diagnostic aspects of cystic fibrosis have been extensively reviewed, with an emphasis on neonatal screening. This systematic literature review involved a search for relevant contributions in the PubMed and SciELO databases. The first references to cystic fibrosis date to the Middle Ages. Cystic fibrosis is the most frequent autosomal recessive hereditary disease among Caucasians (1:2,000 to 3,500). More than 1,000 mutations lead to the disease, the most common being ΔF508, with 70% prevalence among Canadian, Northern European, and American Caucasians and 23 to 55% prevalence among Brazilians. The basic defect is in chloride ion secretion. Cystic fibrosis screening has long been controversial, and after almost three decades, there are few nationwide programs (most are regional or local). However, the U.S. Centers for Disease Control and Prevention (CDC) has concluded that screening for cystic fibrosis is justified. The lack of a specific screening test and the ethnic heterogeneity of the Brazilian population pose challenges for neonatal screening. Cystic Fibrosis; Neonatal Screening; Review Cystic fi brosis and neonatal screening Fibrose cística e a triagem neonatal REVISÃO REVIEW Rodrigues R et al. S476 Cad. Saúde Pública, Rio de Janeiro, 24 Sup 4:S475-S484, 2008 coviscidosis 2. Andersen and Hodges showed for the first time in 1946 that the disease had a genetic origin and resulted from an autosomal recessive mutation 1. The year 1948 witnessed a strong heat wave in New York, and a high incidence of “prostration” was observed in patients treated at Columbia Hospital. Based on careful observation by a young pediatrician, Paul di Sant’Agnese, children with prostration presented a diagnosis consistent with cystic fibrosis. He further observed that these children had abnormal sweat, with high concentrations of sodium and chloride 3. The sweat chloride test was standardized by Gibson & Cooke 4 in 1959 and is still considered the gold standard for diagnosing the disease. In 1979, Crossley 5 demonstrated the increase in plasma trypsinogen (IRT, immunoreactive trypsin), thus providing a practical method that is still used for neonatal screening of cystic fibrosis. In the early 1980s, Paul Quinton 6 and team began to unveil the basic defect in chloride ion secretion. Soon afterwards, researchers led by Francis Collins at the University of Michigan and Lap-Chee Tsui and Jack Riordan at the Hospital for Sick Children in Toronto located the gene for cystic fibrosis in the long arm of chromosome 7, which was cloned and sequenced 7,8,9. This discovery allowed more accurate diagnosis of the disease and better understanding of the clinical disorders it causes and the impact of the deficiency on its protein product, the cystic fibrosis transmembrane conductance regulator (CFTR).