Mukoviszidose: Genetik, Diagnostik und CFTR-Modulatoren

Die Mukoviszidose ist eine generalisierte Systemerkrankung der exokrinen Drüsen. Betroffen sind in erster Linie Atemwege, Leber, Gallenwege, Intestinal- und Reproduktionstrakt. Unbehandelt versterben die meisten Patienten in den ersten Lebensjahren. Dieser Beitrag informiert über die aktuellen Entwicklungen in Diagnostik, Therapie und Management der Mukoviszidose seit Einführung des Neugeborenen-Screenings und der Triple-CFTR-Modulator-Therapie.

Schlüsselwörter

CFSPID - CFTR - CFTR-assoziierte Erkrankung - CFTR-RD - CFTR-Modulator - Elexacaftor - Ivacaftor - Lumacaftor - Mukoviszidose - Schweißsekretionstest - Tezacaftor

• Literatur

• 1 Shteinberg M, Haq IJ, Polineni D. et al. Cystic fibrosis. Lancet 2021; 397: 2195-2211
• 2 Mutation-specific Therapies in cystic Fibrosis. Tümmler B. 2. Bremen: UNI-MED; 2022
• 3 Tümmler B. Mukoviszidose. Pädiatrie up2date 2018; 13: 43-65
• 4 CF-Manual. Ballmann M, Smaczny C, Sutharsan S, Dittrich AM. 3. Stuttgart: Thieme; 2022
• 5 Tümmler B, Storrs T, Dziadek V. et al. Geographic distribution and origin of CFTR mutations in Germany. Hum Genet 1996; 97: 727-731
• 6 Dörk T, Mekus F, Schmidt K. et al. Detection of more than 50 different CFTR mutations in a large group of German cystic fibrosis patients. Hum Genet 1994; 94: 533-542
• 7 Sosnay PR, Siklosi KR, Van Goor F. et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 2013; 45: 1160-1167
• 8 Claustres M, Thèze C, des Georges M. et al. CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants. Hum Mutat 2017; 38: 1297-1315
• 9 Pallenberg ST, Junge S, Ringshausen FC. et al. CFTR modulation with elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis assessed by the β-adrenergic sweat rate assay. J Cyst Fibros 2022; 21: 442-447
• 10 Berg P, Sorensen MV, Rousing AQ. et al. Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis. Ann Intern Med 2022; 175: 1543-1551
• 11 Mathiaparanam S, de Macedo AN, Gill B. et al. Rapid chloride and bicarbonate determination by capillary electrophoresis for confirmatory testing of cystic fibrosis infants with volume-limited sweat specimens. J Cyst Fibros 2023; 22: 66-72
• 12 Stahl M, Steinke E, Graeber SY. et al. Magnetic Resonance Imaging Detects Progression of Lung Disease and Impact of Newborn Screening in Preschool Children with Cystic Fibrosis. Am J Respir Crit Care Med 2021; 204: 943-953
• 13 Castellani C, De Boeck K, De Wachter E. et al. ECFS standards of care on CFTR-related disorders: Updated diagnostic criteria. J Cyst Fibros 2022; 21: 908-921
• 14 Sermet-Gaudelus I, Girodon E, Vermeulen F. et al. ECFS standards of care on CFTR-related disorders: Diagnostic criteria of CFTR dysfunction. J Cyst Fibros 2022; 21: 922-936
• 15 Barben J, Castellani C, Munck A. et al. Updated guidance on the management of children with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID). J Cyst Fibros 2021; 20: 810-819
• 16 Davies J, Sheridan H, Bell N. et al. Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Lancet Respir Med 2013; 1: 630-638