Abstract
Over 50% of Czech patients with cystic fibrosis are currently treated with a triple combination of CFTR modulators (elexacaftor /tezafactor/ivacaftor; ETI) which is the newest and at the same time the most effective drug therapy for patients from the age of 6 years with the pathogenic variant (previously called "mutation") F508del on at least one of the alleles of the CFTR gene. Our case report confirms the dependence of the clinical benefit of CFTR modulator therapy on the "complex" CFTR genotype and the important role of sweat chroride concentration (SCC) monitoring.
In ETI-treated cases where SCC do not decrease as expected and poor patient adherence is excluded, it is advisable to perform CFTR gene sequencing due to the unclear frequency of such complex alleles. Thus, the complex allele L467F-F508del was detected in our 10-year-old boy (genotype L467F-F508del/A72D) that is considered a likely cause in CF patients with non-response to CFTR modulators, especially in cases where the "other" CFTR variant in trans is not amenable to CFTR modulators, as is our case of missense mutation A72D.
As nutritional status and a general sense of well-being of our patient significantly imporved, as well as clinically meaningful improvements in respiratory-related quality of life and lung function were observed, the mere presence of such complex alleles is not an arbitrary reason for CFTRm discontinuation.