J 2024

Case report of two adults with F508del/3849+10 kb C > T genotype regaining exocrine pancreatic function following treatment with elexacaftor/tezacaftor/ivacaftor

ŠŤASTNÁ, Nela and Eva POKOJOVÁ

Basic information

Original name

Case report of two adults with F508del/3849+10 kb C > T genotype regaining exocrine pancreatic function following treatment with elexacaftor/tezacaftor/ivacaftor

Authors

ŠŤASTNÁ, Nela (203 Czech Republic, belonging to the institution) and Eva POKOJOVÁ (203 Czech Republic, belonging to the institution)

Edition

Journal of Cystic Fibrosis, AMSTERDAM, ELSEVIER, 2024, 1569-1993

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30203 Respiratory systems

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.200 in 2022

Organization unit

Faculty of Medicine

DOI

UT WoS

001303160100001

Keywords in English

Cystic fibrosis; Exocrine pancreatic insufficiency; Elexacaftor/tezacaftor/ivacaftor

Tags

Tags

International impact, Reviewed
Změněno: 23/9/2024 13:45, Mgr. Tereza Miškechová

Abstract

V originále

Cystic fibrosis (CF) is a quality-of-life-limiting disease due to multiorgan complications. Exocrine pancreatic insufficiency (EPI) is one of the most common characteristics of CF. Pancreatic function depends on a CFTR gene mutation's class. The milder mutation carriers confer a dominant effect on the exocrine pancreatic status. EPI typically occurs in people who carry two severe mutations, while pancreatic sufficiency typically occurs in either both mild or mild + severe mutation carriers. F508del belongs to a II. class of CFTR pathogenic variant, which leads to reduction of CFTR protein function. 3849+10 kb C > T is in a class V, which is related to reduction in protein quantity. This pathogenic variant is considered mild according to the pancreatic insufficiency prevalence score; carriers of mild genotypes have a significant increase in risk of developing pancreatitis at any age. Carriers of this mutation combination are likely pancreatic sufficient, however, these patients may develop chronic pancreas inflammation and EPI in adulthood. Fecal elastase (FE-1) 〈 100 μg/g together with the clinical signs is considered as EPI, 100 – 200 μg/g is considered borderline and 〉 200 μg/g indicates sufficient pancreatic function. It is widely thought to be irreversible in adults, and might be restored in the youngest children in the case of targeted therapy use. The modest improvement of frequency and severity of gastrointestinal symptoms in CF was reported after CFTR modulator use, but to date, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor (ETI) combinations have not been demonstrated to affect exocrine pancreatic function in adults. Here, we present 2 cases of adult CF patients who improved their pancreatic function serum values after ETI commencement.