Follow-up question M470V

Question

http://ecorn-cf.eu/index.php?id=65&L=0&tx_expertadvice_pi1[showitem]=1410&tx_expertadvice_pi1[search]=Mutation%20V470M%20homozygous

[Note from ECORN-CF team: the above link will lead you to the original question of July 21, 2011.]

Dear experts,

The baby was born on February 1 of this year weighing 3280 g. After 4-5 days we noticed that she had difficulty breathing. The paediatrician said this was nothing out of the ordinary in newborns. She had shortness of breath, the skin around the lips turned blue, and she gained 100 g per week at the most. On May 3, a sweat test was performed at the children’s hospital; the result was 27 mmol/l. In mid-May, the paediatricic pulmonologist prescribed her salbutamol and budesonide. At the end of May / beginning of June, the sweat test was repeated twice at Istanbul University Hospital; 62 mmol/l and 26 mmol/l. Right after this, the pancreatic elastase value in the stool was measured; the result was >500 µg/g. The result of the genetic analysis came on July 4: V470M mutation, not M470V!! If I hadn’t asked the question here, I would probably never have learned that there was a typo in the result. The genetic analyses in Turkey are probably a bit better than those in Kenia or Ethiopia. Currently, my niece is being treated at Marmara University Hospital. She keeps inhaling the above drugs. Since at 7 months she only weighs 5500 g (despite adding 5g maltrodextrin to each meal), she has been getting 4x4000 units of Creon® (pancreatin) per day for two days now, even though, with a pancreatic elastase value of >500 µg/g, there is probably no pancreatic infsufficiency?

The sweat test by way of pilocarpine iontophoresis will be repeated at Marmara University Hospital next year as soon as the bureaucratic obstacles with the Turkish Ministry of Health are settled. Unfortunately I cannot say whether the results of the sweat tests done so far are reliable. On the other hand, I can say without hesitation that the genetic analyses of CF individuals are catastrophic.

I would like to have a detailed genetic test done in Germany, but unfortunately I do not know how the procedure works; how, where and if at all a blood sample can be sent to Germany?

Kind regards.

Answer

Hello,

In the first answer from our expert team, you were already informed that the genetic variation found with your niece was quite a common polymorphism that cannot cause cystic fibrosis. You are saying that the first sweat test, which was carried out at a children’s hospital, was normal with a result of 27 mmol/l. Two further sweat tests taken at Istanbul University Hospital yielded one normal result with 26 mmol/l and one that was more than twice as high, with a slightly elevated value of 62 mmol/l. At the same time, you are saying that the pancreatic elastase was normal at >500. These results you are reporting give reason to the following interpretation:

1) Your niece does not suffer from cystic fibrosis.

2) The one slightly elevated sweat test of Istanbul University Hospital was carried out incorrectly. The other two results, which are very close to each other (26 and 27 mmol/l), confirm that your niece does not suffer from cystic fibrosis. The significant variation in the results from the hospital in Istanbul is always a sign for bad quality of the test procedure!

3) Your child’s insufficient thriving is thus caused neither by cystic fibrosis nor by pancreatic insufficiency. You therefore have to look for other causes of her failure to thrive (among other things, this could be poor quality of the breast milk in case she is being breastfed; problems with nasal respiration; other metabolic disorders; …).

In conclusion, you mention that you would like to have a “detailed genetic test done in Germany.” As it is almost entirely certain that your niece does not suffer from cystic fibrosis, I would like to advise you against this plan. In case you would like to do it nevertheless, here are some considerations:

1) The analysis of the 36 most frequent mutations in CF patients in the Central European population costs between 200,- and 500,- EUR, depending on the laboratory.

2) A so-called complete sequencing of the cystic fibrosis gene costs about 8000,- EUR.

3) You can find the addresses of human genetic institutes at German university hospitals on the internet. You would then have to talk to the laboratory of your choice about the regulations for the transport of the blood sample.

We hope to have calmed you down a bit with our further answer and that your niece will feel much better soon.

Kind regards
Dr. H.-G. Posselt

27.10.2011

27.10.11
Concerning the potential other causes that might lead to the clinical picture of the child: it was reported that she has difficulties in breathing and was blue after birth, and she is not properly gainig weight. I wonder if it has been looked for a congential heart anomality (e.g. to exclude a defect of the atrial or ventricular septum). In order to rule that out, an ultrasoud of the heart (echocardiography) would be advisable.

D. d'Alquen