IRT/DNA - does this mean my son definitely has CF

[TJ22]

Just got back my IRT/DNA results and a sweat test was ordered.

His IRT was 84.9 but his dna test lists as deltaF508/unknown.

I have been scouring the web after my incompetent pediatrician told me he is most likely a carrier. Well my understanding that he would listed as deltaF508/normal if he were heterozygous.

From a document I located on nomenclature deltaF508/unknown is a presumed compound heterozygous or a fluffy term for yes your son has CF.

Any input is greatly appreciated.

 

[Printer]

There are almost 2000 known mutations, any two (2) will cause CF. There are many levels of screening for these mutations, For example a newborn screening is for only 39 mutations. Another is for about 100. Your son needs to have a FULL CF SEQUENCING. The results of which would confirm his CF and also confirm his ability to benefit from new drugs.

You didn't say where the tests were done so I will say, he needs to be treated at an APPROVED CF CENTER by an CF SPECIALIST.

Bill

 

[TJ22]

Thanks for the reply. At this point I was looking for comfirmation the line "deltaf508/unknown" means he has some form of CF. I just got the results Friday at 5pm, so everything is closed and I cant get any conclusive answers. The next step is a sweat test and from what I read that test is not always helpful. I am aware of the full sequencing, but I just wanted to know if I can hold out hoping he is ok or if i should just start planning now for his care.

 

[CrisDopher]

TJ, the sweat test is still the gold standard, despite what any genetic testing may reveal. Although research and treatment is trending toward it, we're not treating chromosomes - we're treating a collection of symptoms that add up to a disease. These symptoms all have in common the salt imbalance that sweat testing reveals. And in many cases, people don't know their mutations or results have been inconclusive, but they're diagnosed with and treated for CF anyway based on the actual presentation of their problems. It's important to remember that and not get hung up on genetics.

However, I would say that since DeltaF508 has been revealed and it seems your son has symptoms of CF, too, that he most likely has it -- as most carriers do not show symptoms at all -- and that any good CF center will initialize CF treatment based on his medical history, not his gene sequencing.

 

[TJ22]

TJ, the sweat test is still the gold standard, despite what any genetic testing may reveal. Although research and treatment is trending toward it, we're not treating chromosomes - we're treating a collection of symptoms that add up to a disease. These symptoms all have in common the salt imbalance that sweat testing reveals. And in many cases, people don't know their mutations or results have been inconclusive, but they're diagnosed with and treated for CF anyway based on the actual presentation of their problems. It's important to remember that and not get hung up on genetics.

However, I would say that since DeltaF508 has been revealed and it seems your son has symptoms of CF, too, that he most likely has it -- as most carriers do not show symptoms at all -- and that any good CF center will initialize CF treatment based on his medical history, not his gene sequencing.

The only "symptom" he has is his irt was "high" at 84.9. His stools are normal, hes not coughing or wheezing, hes gaining weight (over his birth weight at 2 weeks and hes breastfeeding, and he doesnt taste salty to me.

Are you saying despite the dna test that if his sweat test is normal he could possibly be ok?

 

[Julie7]

This must be a difficult time for you, especially getting partial information on a weekend. Keep doing what you are doing, breastfeeding is giving him immunities and it sounds like he is doing well. Like Printer said, the results you received were likely a standard panel, depending upon where you live. You can google what state you live in (assuming you are in the US) and read what newborn screening entails as some states do more than others. Enjoy your baby, take one day at a time and arm yourself with knowledge like you already are. I would say though, every CF patient is different and do not believe everything you read, everyone is different even say twins with exact same mutations. Sounds like your son is lucky to have you as a parent. Wish I could be more helpful. You have come to the right place, this forum is full of great people and tons of knowledge.

 

[2005CFmom]

This is just a guess on my part but I wouldn't worry too much about the deltaF508/normal vs deltaF508/unknown at this point. It could be just different designations from different companies that run the test. Or even since he just had DNA screening the 2nd mutation is "unknown"... don't know if it is normal or a mutation because full sequencing was not done. Upon full sequencing maybe the deltaF508/normal would be noted if no other mutation is found. Get the sweat test and watch for symptoms, but most of all- enjoy that baby of yours!

 

[TJ22]

As I suspected. I called the lab and unknown means and unknown mutation. So unless the lab is wrong or mixed up my sample (both highly unlikely) my son has two mutation and CF. I will now no longer be using my pediatrician who either or unknowingly decided to give me false hope that he is just a carrier. Now I wait for the sweat test.

As for the Ambry Amplified, is it possible to force my doctor to do this or can I order it myself. I realize that route would be absurdly expensive but I don't care.

 

[Aboveallislove]

Dear Mom,
I am so sorry, but one thing I did want to throw out there is that there is already one drug approved by the FDA that can help about 4% of the mutations and probably that will be up to 15% within 6 months or so and another drug that helps "fix" the underlying mutation defect that will likely be to market in 2 years. I know how horrible this time is and felt the same way when I was told "presumptively positive" and asked does he have CF and no one would say "yes," when know in retrospect he had it and they knew since he was homozygous ddf508 and was told it is a screaning and to wait on sweat test. hang in there.
hugs and prayers,
Love

 

[TJ22]

Its actually Dad, but thanks. I did more research and I found the CFTR2 database: http://www.cftr2.org/. They have so far studied 171 mutations of the 1900+ and of those they list 7 as "non Cf-causing mutations" and 15 as "varying clinical consequence" adding up to 22 mutations I can hope for (well I will be hoping for one of the 7). My son is unknown on a test of 33 and of those 33 only one is in the list of 22. To make a long story short there are 21 gene remaining that I can hope and pray my son has along with praying his sweat test comes back normal. At least that can get me to Thursday (the day of his sweat test).

I realize this is a long shot at (22/1900+) but so was him getting 2 mutations (1/3000).

 

[Aboveallislove]

sorry dad. . .lots of moms on here. if you are interested i posted a summary of the first clinic visit what happens from sweat test on . . . if you can't find i'll try to find later. i'd insist n full sequencing and they should do. and i don't think you are being unrealistic--it could be non disease causing. ds had horrible gas at that age and difficulty gaining weight. you can also try putting hand in water and seeing how long until fingers wrinkle...cf is like 3 minutes, casrrer 7 non 10. ds wrinkled horribly in 1 minute flat. not full proof but knowing what i know now, i'd be doing that too wile waiting on sweat test. did they say to gve somr salt in bottle b/f testa?

 

[Printer]

OK hold on. Right now he has only one (1) known mutation. He would need two (2) to have CF. Unknown simply means that they have the results from a very small universe. In that universe he has one known mutation. What is unknown is does he have a second mutation from the "1900+ universe and we don't know the answer to that question. The Doctor is just saying; he has one mutation and we don't know if he has another (unknown).

More testing will be required before you have your answer.

Bill

 

[2005CFmom]

Glad to see you are trying to remain positive and hopeful.

I would be interested to know how the lab determines that there is an "unknown" mutation. I could understand if your baby was already diagnosed with CF based on sweat test and symptoms. But you just have a high IRT which does produced false positive results. If there is a diagnosis of CF and then a DNA test reveals only one mutation, the other mutation is "unknown" because you have a diagnosis therefore there has to be two mutations.

On a DNA screening (without a confirmed CF diagnosis) how can they tell there is an "unknown" mutation? I have never heard of them being able to tell via blood test that there is a mutation, but they don't know what it is. They either find it and are able to name it, or the gene is negative for the tested mutations. I don't know if my question is making sense to you. But if you are able to find out these answers and post it may teach us all something. Then we can be more helpful to others with same questions in the future.

Could the lab be in error thinking that they were running a test on a confirmed CF patient instead of just doing a screening?

In any case, I am happy that the sweat test is Thursday and you don't have to wait weeks. Regardless of what the test reveals, I would ask if you could be referred to an approved CF clinic since you have received conflicting information.

 

[Aboveallislove]

teri nailed it.

 

[Printer]

Teri, Love:

We need to note where these tests were done. A local pead did a "screening sweat test" not the same sweat test that is done in a CF Center. False positives for this scan are very common. All that we do know for certain is that he has one mutation. The world is full of Doctors who can't even spell CF much less Dx or treat it.

He needs to go to a CF Clinic ASAP.

Bill

 

[Aboveallislove]

Bill, maybe I missed it, but I don't think anyone did sweat test yet. It was newborn screen that came up with high it and DNA was my understanding, which is why I think Teri is right re why lab said unknown mutation ...like you said they aren't testing for many so how would they know that there is an unknown mutation.

 

[WildCherry]

I have tried to PM you 3 times with our story but I can't so I'll post it here. My goal was to give you hope that yes, you can hold hope that your baby is fine even with an elevated IRT. Honestly your baby's IRT wouldn't have even been flagged for the DNA screen in the state I live in. My son had an elevated IRT and they found a copy of DF508. Sweat test at one month came back at 30. One measly point into the borderline range for that age. We had a full gene sequence which found R1162L which has unknown clinical significance so they have no idea if it even causes disease. A second Sweat test at 6 months of age came back normal at 15. We just had his one year follow up and we were sent to a urologist who confirmed that baby boy has both vas deferens. My son is not diagnosed with CF or CRMS. Our CF pulmonologist says if he could do one thing he would like to go back and not have us do the sweat test at 1 month but to have waited a couple months. He's confident that we are not looking at CF but it took all this effort to get here becasue of a slightly elevated newborn screen. My son is healthy, has no signs or symptoms of CF and I think the doc only has us come back to cover his own butt should something come up in the future. I hope your baby's sweat test yeilds a normal result on Thursday and that you don't have to go through the rigamarole that we do even though our child is perfectly healthy. IRT's can be elevated for many reasons! Good luck to you and should you have to follow a similar path we did please feel free to reach out to me.

 

[2005CFmom]

Bill,

Glad to see you agree with me.

Glad to see you are trying to remain positive and hopeful.

... But you just have a high IRT which does produced false positive results. ...

... Regardless of what the test reveals, I would ask if you could be referred to an approved CF clinic since you have received conflicting information.

Teri

 

[Printer]

Love:

You are right. Just more reason to slow down. All that we know now is that this kid is a carrier.

Bill

 

[Aboveallislove]

Bill,
I think the confusion is that the lab told this guy that the other mutation was an "unknown mutation" as oppose to that they just found 1 mutation. And that the report said the df508 and "unknown mutation" as oppose to just df508. Logically it would seem they used that terminology for a reason. I know with DS's diagnosis, I got a called at 11 days old from the newborn screening office and they asked for ped telephone #. I was half asleep and asked if anything of concern. They said just one thing. I said what and they said he was "presumptively positive for CF." I hung up and as my eyes closed, I jumped because the "presumptively" stuck out. . . a "positive" screen, I was not concerned with b/c I know what screening means, but that she said "presumptively positive," made me realize that it wasn't just a screen. The ped unfortunately wasn't frank with me and said it was a screen even though he had homozygous ddf508 noted, which as I now know means CF. So I can see what the dad thinks this is CF because they said "unknown mutation," which would seem to mean something. That's why I think Teri nailed it. . . the lab might have put that because they thought they were screening for 2 mutations and when the second one wasn't in the 30some it tests they put unknown. We could be wrong. . . maybe they can tell there is a mutation and just not know what it is, but I wouldn't think so. Dad, please do update us so we all know in the future and hang in there.