Intermediate sweat test

Question

Hello,
I ask myself a lot of questions after reading one of your answers to a subject. You said in this response that the sweat test should be less than 30 µmol/l.
My 16-months-old daughter has CF (diagnosed at 1 month) with a DF508 mutation and another mutation of class 5 G3272-26A and a sweat test at 75 ... She is currently moderate pancreatic insufficient with 167 for the last fecal analysis. She has no weight or growth problems and ther stool is "normal".
The sweat tests performed on my 4-year-old son at the CF Center were 34 and 35 µmol. The Professor of the CF center told me that our son was not suffering from CF. At the time of his birth in 2010, he had performed the Guthrie test and I think it was negative as we had not been contacted.
He is now 5 years old and has had a lot of bronchitis since birth in the winter. We put it down to the school etc, but reading your answer, I ask myself questions knowing that my daughter has two specific mutations. My son has a growth curve excellent view above the norm.
Is it possible that my son has cystic fibrosis?

Answer

Hello,

Your boy has had some bronchitis during the winter like many children who are not suffering from CF. His neonatal CF screening test was a priori negative because you have not been contacted by the screening center and he seems to be doing pretty well with growth above the norm. Moreover, in the international CFTR2 database which includes clinical and genetic data of more than 60,000 patients, 457 patients with your daughter’s genotype (F508del / 3272-26G-> A), have an average sweat test of 94mmol / L, thus clearly positive.

It is therefore very unlikely that your boy has CF but not detected by the screening test (false negative frequency of CF neonatal screening is about 5%).
However, even though the probability your boy has CF is very low, this possibility has to be ruled out for reassuring you. The most radical solution would be to get a drop of your boy’s blood in order to search for CFTR mutations and particularly the 2 mutations his sister is carrying.
The most likely explanation of your boy's intermediate sweat test (almost negative) is that he is (like his parents) healthy carrier of a single CFTR gene mutation: the probability is 1 in 2. Sweat chloride is actually higher in healthy carriers of a single mutation than in individuals carrying no CFTR gene mutation.

Hope this answer can help.
Best wishes

Gilles RAULT, MD, Roscoff CF Center

01.02.2016