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.