Refining the continuum of CFTR-associated disorders in the era of newborn screening. Clin Genet 2016 May;89(5):539-49
Date
12/17/2015Pubmed ID
26671754Pubmed Central ID
PMC5389888DOI
10.1111/cge.12711Scopus ID
2-s2.0-84955259453 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Clinical heterogeneity in cystic fibrosis (CF) often causes diagnostic uncertainty in infants without symptoms and in older patients with milder phenotypes. We performed a cross-sectional evaluation of a comprehensive set of clinical and laboratory descriptors in a physician-defined cohort (N = 376; Children's Hospital of Wisconsin and the American Family Children's Hospital CF centers in Milwaukee and Madison, WI, USA) to determine the robustness of categorizing CF (N = 300), cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (N = 19), and CFTR-related (CRMS) metabolic syndrome (N = 57) according to current consensus guidelines. Outcome measures included patient demographics, clinical measures, sweat chloride levels, CFTR genotype, age at diagnosis, airway microbiology, pancreatic function, infection, and nutritional status. The CF cohort had a significantly higher median sweat chloride level (105 mmol/l) than CFTR-related disorder patients (43 mmol/l) and CFTR-related metabolic syndrome patients (35 mmol/l; p ≤ 0.001). Patient groups significantly differed in pancreatic sufficiency, immunoreactive trypsinogen levels, sweat chloride values, genotype, and positive Pseudomonas aeruginosa cultures (p ≤ 0.001). An automated classification algorithm using recursive partitioning demonstrated concordance between physician diagnoses and consensus guidelines. Our analysis suggests that integrating clinical information with sweat chloride levels, CFTR genotype, and pancreatic sufficiency provides a context for continued longitudinal monitoring of patients for personalized and effective treatment.
Author List
Levy H, Nugent M, Schneck K, Stachiw-Hietpas D, Laxova A, Lakser O, Rock M, Dahmer MK, Biller J, Nasr SZ, Baker M, McColley SA, Simpson P, Farrell PMAuthor
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentChild
Chlorides
Cohort Studies
Cross-Sectional Studies
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Female
Genetic Testing
Genotype
Hospitals, Pediatric
Humans
Infant
Infant, Newborn
Male
Mutation
Neonatal Screening
Pancreas
Pseudomonas aeruginosa
Sweat
