Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis
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Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis : validation and reference data. / Derichs, Nico; Sanz, Javier; Von Kanel, Thomas; Stolpe, Cornelia; Zapf, Antonia; Tümmler, Burkhard; Gallati, Sabina; Ballmann, Manfred.
In: THORAX, Vol. 65, No. 7, 07.2010, p. 594-599.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis
T2 - validation and reference data
AU - Derichs, Nico
AU - Sanz, Javier
AU - Von Kanel, Thomas
AU - Stolpe, Cornelia
AU - Zapf, Antonia
AU - Tümmler, Burkhard
AU - Gallati, Sabina
AU - Ballmann, Manfred
PY - 2010/7
Y1 - 2010/7
N2 - BACKGROUND: In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).OBJECTIVES: To describe reference values and validate ICM for the diagnostic classification of questionable CF at all patient ages.METHODS: ICM was performed in 309 rectal biopsies from 130 infants, children and adults including patients with known pancreatic-insufficient (PI)-CF (n=34), pancreatic-sufficient (PS)-CF (n=7), patients with an unclear diagnosis with mild CF symptoms, intermediate sweat test and/or CFTR mutation screening (n=61) and healthy controls (n=28). ICM was correlated to sweat chloride, extensive CFTR genotype and transcript analysis in the diagnostic group. The results were compared with previous ICM data in subjects with CF, congenital bilateral absence of the vas deferens, heterozygotes and controls.RESULTS: The cumulative chloride secretory response of DeltaI(sc,carbachol), DeltaI(sc,cAMP/forskolin) and DeltaI(sc,histamine) was the best diagnostic ICM parameter (cut-off 34 muA/cm(2) between patients with known PS-CF and controls), differentiating patients with questionable CF into PS-CF (n=6) and 'CF unlikely' (n=55) groups. Extensive genotype analysis detected two mutations (40% disease-causing) in 100% of individuals classified as PS-CF compared with 1.8% in those classified as 'CF unlikely'.CONCLUSIONS: This comprehensive investigation of CFTR function and genotype underlines the diagnostic value of ICM, especially for confirmation of CF in the absence of two disease-causing CFTR mutations, exclusion of CF despite intermediate sweat test and age groups unsuitable for nasal potential difference measurements. ICM is an important tool for functional assessment in CFTR mutations of unknown clinical relevance.
AB - BACKGROUND: In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).OBJECTIVES: To describe reference values and validate ICM for the diagnostic classification of questionable CF at all patient ages.METHODS: ICM was performed in 309 rectal biopsies from 130 infants, children and adults including patients with known pancreatic-insufficient (PI)-CF (n=34), pancreatic-sufficient (PS)-CF (n=7), patients with an unclear diagnosis with mild CF symptoms, intermediate sweat test and/or CFTR mutation screening (n=61) and healthy controls (n=28). ICM was correlated to sweat chloride, extensive CFTR genotype and transcript analysis in the diagnostic group. The results were compared with previous ICM data in subjects with CF, congenital bilateral absence of the vas deferens, heterozygotes and controls.RESULTS: The cumulative chloride secretory response of DeltaI(sc,carbachol), DeltaI(sc,cAMP/forskolin) and DeltaI(sc,histamine) was the best diagnostic ICM parameter (cut-off 34 muA/cm(2) between patients with known PS-CF and controls), differentiating patients with questionable CF into PS-CF (n=6) and 'CF unlikely' (n=55) groups. Extensive genotype analysis detected two mutations (40% disease-causing) in 100% of individuals classified as PS-CF compared with 1.8% in those classified as 'CF unlikely'.CONCLUSIONS: This comprehensive investigation of CFTR function and genotype underlines the diagnostic value of ICM, especially for confirmation of CF in the absence of two disease-causing CFTR mutations, exclusion of CF despite intermediate sweat test and age groups unsuitable for nasal potential difference measurements. ICM is an important tool for functional assessment in CFTR mutations of unknown clinical relevance.
KW - Adolescent
KW - Adult
KW - Child
KW - Child, Preschool
KW - Chlorides
KW - Cystic Fibrosis
KW - Cystic Fibrosis Transmembrane Conductance Regulator
KW - Female
KW - Genotype
KW - Humans
KW - Infant
KW - Male
KW - Membrane Potentials
KW - Middle Aged
KW - Mutation
KW - Rectum
KW - Reference Values
KW - Reproducibility of Results
KW - Sweat
KW - Young Adult
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Validation Studies
U2 - 10.1136/thx.2009.125088
DO - 10.1136/thx.2009.125088
M3 - SCORING: Journal article
C2 - 20627915
VL - 65
SP - 594
EP - 599
JO - THORAX
JF - THORAX
SN - 0040-6376
IS - 7
ER -
