Positive sweat test - negative gene test

Question

Hello, I have a 5-year-old daughter which suffers constantly from colds, gastro-intestinal infections and loss of appetite. She weighs 15.6 kg only with a height of 111 cm. 2 years ago my pediatrician had the idea of doing a sweat test. We did this 3 times and all 3 test were positive (far beyond 100). I had this test done in a hospital which is also specialized in CF. The conductivity had been measured, that is what I know. In one of the results however, the chloride content of the sweat had been measured and the value was 112. How reliable is this measurement???

Furthermore, an x-ray of the lungs had been done, which showed little changes, it has been said, the lung was involved minimally. An intolerance of food, an allergy to food, celiac disease or the other things, that could lead to a positive test result had been tested and were negative.

Furthermore the CF-doctor there said to me that it was normal for CF patients that they suffer from loss of appetite. And I have been told, too, that every CF has a different course. One patient has all symptoms, the other only one symptom. My daughter suffers every 2 weeks from a gastro-intestinal infection and I have been told that this is typical for CF, too. We have been told that therefore the diagnosis of CF has been proven.

I have read that many CF-patients have Hippocratic nails, I have seen them in my daughter. I have read yesterday that there is another illness which can be compared to CF and has mostly the same symptoms – cartagener syndrome. Can the sweat test also be positive with this syndrome?

To be on the safe side we have also done a gene test on the 25 most common mutations – negative. The doctor was of the opinion that she might have a more seldom mutation and did a test on the other 800 mutations – negative. For me it is now the question why the sweat tests have been positive in spite of this??

Answer

Hello,

I would answer your questions as follows:
Hello, to your questions we can give the following answers. The height of your daughter lies in the middle normal range for an exactly 5-year-old girl. The weight lies 3 kg below the expected ideal weight concerning her actual height. She is therefore slim but not underweight.

After the 3 positive sweat test results your pediatrician did right and initiated the actual international common diagnostic program. In case of three positive sweat test results over 100, on would expet that the genetic investigations revealed known mutations. Therefore one has to doubt the accuracy of the sweat test method, which had been used. You report that the sweat test had been done at a hospital which is specialized in CF. You report that the sweat test had been measured with the conductivity method. Here it has to be said that this method should not be used in so-called certified CF-centers due to the high rate of mistakes. An investigation with the chloride-meter or the old method of Gibson and Cooke as pilocarpine ionotophoresis with photometric measurement of sodium and chloride in the sweat should be done. This is the gold standard and less interference-prone than the conductivity method. You can not rely on the conductivity method. In general, the diagnosis of CF can not be made out of one single measurement. Therefore, the sweat test has to be repeated with the right method at a certified CF-center. In case the values remain increased, one has search further.

On the one hand, all illnesses which could cause an increased sweat test value, have to be excluded. In the following I have listed all illnesses which can be accompanied by an increased chloride value in the sweat. You should work up this list with your pediatrician, in case the sweat value remains increased after having been assessed with the right method. In this list you do not find the cartagener syndrome, as the sweat test is normal in those patients.

Adrenal insufficiency
Anorexia nervosa
Atopic dermatitis
Autonomic dysfunction
Coeliac disease
Ectodermal dysplasia
Familial cholestasis (Byler’s disease)
Fucosidosis
G6PD deficiency
Glycogen storage disease type 1
Hypogammaglobulinaemia
Hypoparathyroidism
Hypothyroidism
Klinefelter's syndrome
Malnutrition
Mucopolysaccharidosis type 1
Nephrogenic diabetes insipidus
Nephrosis
Pseudohypoaldosteronism
Psychosocial problems

On the other hand, in case of several doubtlessly positive sweat test results, ongoing investigations have to be performed, in order to diagnose a CF or to rule it out. Has the function of the pancreas been tested in your child? As you report a loss of appetite of your child, I assume that the pancreas of your child does work normal. With a sweat test result of 100 one expects that the full picture of CF is there. Then also a hypofunction of the pancreas must be found and this is in the untreated condition always associated with an increase of appetite, unless the lung had already severe damage. This can be excluded according to the normal lung x-ray. This does also not fit into the diagnosis of CF.

You report of frequent gastro-intestinal infections of your child and that the CF doctor said, that this was typical of CF. This statement does not fit the general understanding of the picture of CF. A child with CF has only problems with the GI-tract if there is a hypofunction of the pancreas and/or if the child receives antibiotics frequently. In case the pancreas of your child works normally, the none has to look for another cause of the frequent “gastro-intestinal infections” (e.g. food intolerances like celiac disease, lactase deficiency, fructose malabsoprtion or an immunoglobulin deficiency etc).

In case of doubt, a measurement of the nasal potential difference or Intestinal current measurement (ICM) in biopsates of the rectum at specialized centers could help further.

Last it has to be clarified, if the methods of genetic investigations for the diagnosis of CF have been exhausted completely, that means beside the screening tests, which cover a certain amount of known CF-causing genes, there is the possibility of so-called scanning / sequencing methods, which analyse the gene of interest completely. However it has to be said that even with the most accurate genetic method 1-5% of all CF-alleles (that are the gene loci) remain undetectable, therefore even with that, a CF cannot be excluded with a 100% security.

All the best to you and your child.

Kind regards

H.-G. Posselt

13.09.2010

13.09.10 Altogether 4 Questions on this topic from the same questioner had been posed. This question/answer pair summerizes all questions and answer.
D. d'Alquen