Primary Sclerosing Cholangitis in Childhood is Associated with Abnormalities in Cystic Fibrosis–Mediated Chloride Channel Function

Objective To determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR). Study design Subjects with PSC diagnosed in childhood (n = 20) were recruited from Children’s Hospital. Subjects had testin...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of pediatrics 2007-09, Vol.151 (3), p.255-259
Main Authors: Pall, Harpreet, MD, Zielenski, Julian, PhD, Jonas, Maureen M., MD, DaSilva, Deborah A., RN, Potvin, Kimberly M, Yuan, Xiao-Wei, MSc, Huang, Qiuju, MD, Freedman, Steven D., MD, PhD
Format: Article
Language:English
Subjects:
Adolescent
Biological and medical sciences
Cholangiopancreatography, Endoscopic Retrograde
Cholangiopancreatography, Magnetic Resonance
Cholangitis, Sclerosing - diagnosis
Cholangitis, Sclerosing - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Disease Progression
DNA Mutational Analysis
Errors of metabolism
Female
Gastroenterology. Liver. Pancreas. Abdomen
General aspects
Genotype
Humans
Ion Transport - genetics
Isoproterenol - blood
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Metabolic diseases
Miscellaneous hereditary metabolic disorders
Other diseases. Semiology
Pediatrics
Peroxisome Proliferator-Activated Receptors - physiology
Prospective Studies
Sweat - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective To determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR). Study design Subjects with PSC diagnosed in childhood (n = 20) were recruited from Children’s Hospital. Subjects had testing with sweat chloride concentration, nasal transmembrane potential difference, and extensive genetic analysis of the CFTR gene. Disease control subjects consisted of 14 patients with inflammatory bowel disease alone and no liver disease. t Tests were performed to determine statistical significance. Results In the PSC group, CFTR chloride channel function (ΔChloride free + isoproterenol) was markedly diminished at −8.6 ± 8.2 mV (reference range: −24.6 ± 10.4 mV). In contrast, disease control subjects had normal function, at −17.8 ± 9.7 mV ( P = .008). Sweat chloride concentration in subjects with PSC was greater than in disease control subjects (20.8 ± 3.4 mmol/L vs 12.0 ± 1.6 mmol/L, P = .045). Comprehensive CFTR genotyping revealed that 5 of 19 (26.3%) subjects with PSC had a CFTR mutation or variant, compared with 6 of 14 (42.9%) disease control subjects. Conclusions There is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood PSC.
ISSN:0022-3476
1097-6833
DOI:10.1016/j.jpeds.2007.03.062