CF despite negative gene test?

Question

Hello,

I have a question for you and hope you can help me with it. Our daughter (3 years old now) had to struggle with bronchitis and pneumonia from last fall almost continuously until May/June. Pap smears of the sputum did not provide any conclusions about the reason/germ… She took antibiotics almost constantly, which helped, but the cough and the inflammation always came back shortly after she stopped taking them. She had sudden coughing fits, regurgitated viscous mucus, etc… We inhaled (salbutamol, a cortisone compound, and saline – this helped very well, especially during acute coughing fits).

I have to add that my daughter is very delicate and lightweight and has a hard time gaining weight. Celiac disease and lactose were both negative. Fructose was positive, but we have that under control now…

We did a sweat test, which was at 66, and another one after that, which was only at 36. Since the symptoms pointed to cystic fibrosis, we had a gene test done, which was negative.

Now my question: how reliable is a gene test? Would it be possible that my daughter has CF even with a negative test…? Could it perhaps be a form of CF that cannot be detected with a blood test?

The cough, etc. has been gone since May/June… (our older daughter did not go to kindergarten for a while then… since September she is going again…), and now it started again a week ago… Cough (no fever), she gags when she has a coughing fit at night, etc…

I hope you can provide some help…?!

Answer

Hello,

in principle you are right. With the anamnesis you are describing here, one could and should also consider CF. It was therefore right to do a sweat test. Unfortunately, the test values you are providing do not indicate what exactly was measured. This is important, however, since it is important to know whether the values indicate the chloride proportion in the sweat or whether only the conductivity was measured. The chloride is more telling, and for this both values would have been at medium range (that is, neither positive nor negative). Since you are writing that the second value was “only” 36, I assume that the conductivity was tested – as this would actually be a normal value for it. In this case, a third test should have been done.

Nevertheless, the doctor decided to do a gene test. It needs to be added here that we generally recommend getting clarification from a certified CF center after inconclusive sweat test results. Especially with unclear findings, experience with the disease and also knowledge of possible further diagnostic measures (which cannot be taken everywhere) are invaluable.

But back to your question: In a gene test, around 30 mutations are checked for with ready-made testing kits. These kits contain those mutations that are most common in Central Europe. If the mutations cannot be found with this, the whole CF gene can be sequenced; that is, another, more accurate search will be performed (very expensive). However, these decisions should really be made in a certified CF center (also in order to avoid unnecessary diagnostics and costs). It would indeed be possible that the sequencing will show a gene that the test kit did not. In practice, however, it is very likely to find the two triggering mutations with the test kit. It is also possible to find only one triggering mutation and to then do a sequencing of the CF gene for the second mutation. Theoretically, it is also possible, though rather unlikely in practice, that the kit does not yield any mutation even in case of CF. For your child, in my opinion the following questions should be answered now:
1. How should the sweat test results be classified? What was measured? Should further sweat tests be done?
2. Depending on the answer to this question, it should be decided in what ways the gene test should be supplemented.
3. These results should be evaluated in a certified CF center in your vicinity and discussed with you. In addition, it should be decided whether further diagnostic measures are necessary or, if not, whether and when to examine your child again.
4. At any rate, your child should be monitored in this regard, and other differential diagnoses should be ruled out as well.

Kind regards

Olaf Sommerburg

19.11.2009