Positive sweat test

Question

Hello, I am 29 years old and in 2012 I had two positive sweat tests at 96 mmol / L. Genetic tests have been made by the laboratory from Créteil, but no abnormalities were detected. I have got a significant pulmonary impairment since 1999, including bronchiectasis. Pulmonologists' opinions differ. With only my positive tests, do I have to search for another disease? Thank you.

Answer

Hello,
The positivity of the sweat test (provided that it has been performed in an experienced center measuring the chloride concentration in the sweat using the so-called pilocarpine ionotophoresis) associated with respiratory impairment including bronchiectasis confirms the diagnosis of cystic fibrosis. Most often, two mutations can be identified in the CFTR gene. However, in 1–1.5% of patients with fully expressed disease, no CFTR mutation can be identified. The inability to detect these mutations may be partly explained by the fact that genetic tests mainly study the coding region and the adjacent exon-intron junctions. Mutations located in the intronic and promoter regions as well as in distant regulatory sequences are not routinely screened for, and may therefore be missed.
In addition, we now know that mutations in genes encoding the ENaC epithelial sodium channel may produce a clinical picture of cystic fibrosis in approximately 10% of patients with no identified CFTR mutation. Other genetic factors causing CF-like disease remain unknown.
In your case, it would be interesting to measure nasal potential difference that studies the transport of ions across the airway epithelium and distinguishes the secretion of chloride ions associated with the CFTR channel activity and the absorption of sodium mediated by the EnaC epithelial channel. You could also complete the genetic analysis of the ENaC gene subunits. These tests are feasible at Cochin Hospital in Paris.
Best regards.
Dr Dominique Hubert

28.02.2013