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).


METHODS
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 (deltaChloride 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.
Pall
Harpreet
H
Division of Pediatric Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. harpreet.pall@childrens.harvard.edu
Zielenski
Julian
J
Jonas
Maureen M
MM
DaSilva
Deborah A
DA
Potvin
Kimberly M
KM
Yuan
Xiao-Wei
XW
Huang
Qiuju
Q
Freedman
Steven D
SD
D000293:Adolescent; D002760:Cholangiopancreatography, Endoscopic Retrograde; D049448:Cholangiopancreatography, Magnetic Resonance; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D007545:Isoproterenol / Q000097:blood; D008297:Male; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D011446:Prospective Studies; D013542:Sweat / Q000737:chemistry
D047492:Peroxisome Proliferator-Activated Receptors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007545:Isoproterenol