Case report of two adults with F508del/3849+10 kb C > T genotype regaining exocrine pancreatic function following treatment with elexacaftor/tezacaftor/ivacaftor
Abstract
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. 508del 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.