DISCUSSION:
The diagnostic criteria for cystic fibrosis suggest that there must be both the characteristic clinical phenotype of the disease and also a documented dysfunction of the CFTR protein [1]. The patient of this report cannot be considered a cystic fibrosis patient because he does not have the classic clinical features of the disease, the sweat chloride test has shown indeterminate values and he doesn’t present two known genes or gene variant that causes the disease.
The CFTR-related diseases are those that have association with CFTR gene dysfunction, but do not fulfil the diagnostic criteria for the disease [4]. This new classification is related to the advances in genetic testing that guide the diagnosis criteria for cystic fibrosis and this new group of diseases. In fact, it is still difficult to distinguish those two entities [3], and as new discoveries are made, new classifications systems will be adopted.
Three clinical entities have strong support in the literature, being defined as CFTR-related diseases: bilateral congenital absence of the vas deferens with CFTR dysfunction, recurrent acute pancreatitis or chronic pancreatitis with CFTR dysfunction, and disseminated bronchiectasis with CFTR dysfunction [3]. In addition to these presentations, other phenotypes were observed associated with mutations in the CFTR gene, such as sinusitis and bronchopulmonary allergic aspergillosis [2]. Many of the patients with these phenotypes will never progress to a phenotype of frank cystic fibrosis and, therefore, their follow-up may be done differently from that usually done in patients with cystic fibrosis [3].
The patient reported has a p.Leu1156Phe G>T alteration, in which is observed a guanine to thymine change at nucleotide 3599 in exon 18, which would lead to a replacement of leucine by phenylalanine in the protein sequence at residue 1156 (L1156F) [5]. Although this change is localized in the CFTR gene, it still represents an undetermined meaning mutation [5]. Given the presentation of the reported patient, oligosymptomatic cystic fibrosis with only chronic constipation, indeterminate sweat chloride test and a genetic alteration in the CFTR coding area, without the characterization of frank cystic fibrosis, it is believed that the mutation found, not yet described in the literature, could be related and could be classified as a CFTR-related disease. For more accurate diagnosis, in addition to the sweat test and mutation investigation in the CFTR gene, measurements of nasal potential difference [2] [3] and intestinal current measurement [3] should be performed.