Mutations

Question

One year ago my 20 months old daughter had 2 sweat tests over 200! The screening test was negative at birth. She is considered and treated as CF but has no identified mutation so far ! Nevertheless, she is very symptomatic, has been colonized with Pseudomonas and is pancreatic insufficient. Is there such atypical cases? Is the diagnosis finally assessed?

Answer

The situation of your daughter is actually not common but is nevertheless well known despite the fact that scientific publications in this area are particularly rare. Generally, the diagnosis of cystic fibrosis can be suggested by a positive screening test (this was not the case with your daughter) or by the recognition of symptoms suggestive of the disease (which seems the case with your child that describe as very symptomatic including colonization by Pseudomonas aeruginosa and pancreatic insufficiency). The suggested diagnosis has to be confirmed by the detection of 2 mutations in the cystic fibrosis gene (CFTR) and / or a positive sweat test (ie showing a concentration of sweat chloride > 60 mmol / l) and reliable (ie performed in a specialized center according to the "good clinical practice"). The combination of a positive sweat test and two CFTR mutations is by far the most common situation but there are few proven cases of cystic fibrosis with no identified mutation in spite of a gene analysis called "complete" by an expert laboratory. Nowadays, the methods of molecular analysis explore actually a part of the CF gene (27 exons representing 20,000 base pairs on the 180,000 which constitute the entire gene). These analysis techniques are progressing steadily and it is however possible that we might in the future identify the molecular defect carried by your child. From a practical standpoint, the recommandation is to keep on having your child followed by an acknowledged team of a specialized center.
Hope to have answered your question.
Dr. Gilles Rault (with the contribution of Professor Claude FEREC)

07.04.2011