Adult Onset Cystic Fibrosis, Invitae Cystic Fibrosis Test, MAC, Bronch

Hi, a couple of years ago during a workup I had an Invitae genetic test for immunodeficiencies and for CF. At the time I believe it was over 450+ variants. The genetic testing was chosen by my doctor, an immunologist, who is familiar the panels. I could never have done this on my own. Plus, this way my insurance covered the testing.

Would you be able to meet with your doctor or a specialist—perhaps at a bronchiectasis center—to decide which genetic panel would be most appropriate? Given your health history, genetic testing could be very helpful in guiding a treatment plan, especially with the support of someone trained and experienced in interpreting the results.

Your symptoms, with just a couple of exceptions, are almost identical to mine. I am 77 years old and was diagnosed as having CF just over 4 years ago. I suffered from bronchietasis and repeated lung infections for years, until a pulmonologist at the Mayo Clinic in Jacksonville ordered a sweat test for CF. That came back positive, so they then ordered a DNA test. Shortly after that I received a call telling me that I had CF, and I've been treated in their CF clinic ever since then. They have really helped me so much.

For what it's worth, I too am of Northern European descent.

Actually, my PCP ordered the Invitae Immunodeficiencies Panel - tests 429 genes.

The results were negative

then

My Infectious Disease Specialist referred me to an Immunologist based upon the following blood test

NATURAL KILLER (CD 16+56) PRO - 3 Flagged Low & 2 Flagged High

LYMPH %, FLOW Range: 15 - 40 % Value 11 Flagged Low
CD4 % Value 57 Flagged High
CD8 % Value 13 Flagged Low
CD8 ABS Range: 166 - 1,771 /MCL Value 121 Flagged Low
CD4/CD8 RATIO Range: 1.00 - 2.50 Value 4.48 Flagged High

* Potential symptoms associated with a low CD8 percentage can be general signs of a weakened immune system, such as frequent infections, prolonged recovery from
illness, 'fatigue’, and ‘unexplained weight loss'. However, these symptoms can also be caused by other health conditions.

At my initial 2025 appointment with the Immunologist, he stated that he was unsure as to whether the 3 antibiotics I was being treated for MAC were effective
given my continued symptoms.

At my Immunologisty's blood tests follow up appointment the Immunologist's assessment:

2024 Bronchoscopy documented Candida
- Gentleman in no acute distress but * quite thin
T-cell function tests show subtle abnormalities: CD3 absolute number slightly low at 609 (lower limit 622), increase in natural killer cells, decreased response to Candida and tetanus antigens
* no clear etiology has been identified for the weight loss and inflammatory pain.

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< Would you be able to meet with your doctor or a specialist perhaps at a bronchiectasis center to decide which genetic panel would be most appropriate?>

Actually, I thought about doing such and I will call the Adult Cystic Fibrosis Center of Central Texas again.

< Given your health history,>

My medical history is significantly more extensive that what I initially posted here.

Thank you for your reply post as it has been helpful to me.

< Your symptoms, with just a couple of exceptions, are almost identical to mine. I am 77 years old and was diagnosed as having CF just over 4 years ago.>

* That is very helpful to know.

I read other Mayo Clinic Cystic Fibrosis discussion topics posts and there are 70s and 80s years olds that were diagnosed with CF late in life.

My online research revealed

Cystic fibrosis (CF) can occur in families without a known history of the disease, as both parents may be carriers of the CF gene without showing symptoms.

The first attempts at newborn screening (NBS) for Cystic fibrosis were performed in the 1970s, but widespread implementation was not realized until the late 1980s and early 1990s.

I am 70 years old

Cystic fibrosis isn’t diagnosed in some people who have mild symptoms 'until they’re adults'. This is known as * Adult Onset Cystic Fibrosis. * Cystic fibrosis can be diagnosed in older adults through a combination of clinical evaluation, sweat tests, and genetic testing to identify mutations in the CFTR gene. Symptoms may include chronic 'respiratory issues' and 'digestive problems', which 'can lead to a delayed diagnosis until adulthood'.

< For what it's worth, I too am of Northern European descent.>

* That is helpful to know as well.

FWIW

Years ago, my left hand pinky finger froze. My PCP referred me to an Orthopedic Hand Surgeon.

I was diagnosed with Dupuytren disease. I declined the corrective surgery.

Dupuytren contracture is characterized by a deformity of the hand in which the joints of one or more fingers cannot be fully straightened (extended); their mobility is limited to a range of bent (flexed) positions. The condition is a disorder of connective tissue,

Dupuytren's contracture occurs in about 5% of people in the U.S. The condition is 3 to 10 times more common in people of European descent than in other groups. Sometimes the condition is called "Vikings' Disease."

In men, Dupuytren's contracture most often occurs after age 50.

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Years, later I developed a frozen left shoulder.

Severe Dupuytren disease may also be associated with frozen shoulder (adhesive capsulitis of shoulder),

My PCP referred me to an Orthopedic Surgeon.

I was treated with steroid injections and physcial therapy.

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< I've been treated in their CF clinic ever since then. They have really helped me so much.>

Yesterday, the Adult Cystic Fibrosis Center of Central Texas representative told me if I tested positive for Cystic Fibrosis, she could talk for 40 minutes on the possible treatments.

Thank you for your reply post.

I had the CFTR 508 First Plus Reflex test. I have a lot of the symptoms of CF and my pulmo says he has only seen BE and Pseudomonas as bad as mine in his CF patients. But it was negative.

Ai tells me that CFTR 508 First Plus Reflex test tests for the most common mutation whereas the Invitae is much more robust and looks for many many different variants. Sorry to complicate things for you @irenea8 ....

Specifically, "If you need a comprehensive result (diagnosis, carrier status across diverse ancestries, identification of variants that guide CFTR-modulator therapy, or if there’s clinical suspicion despite a negative single-variant screen), go with full-gene testing such as Invitae’s CFTR panel."

< I had the CFTR 508 First Plus Reflex test. I have a lot of the symptoms of CF and my pulmo says he has only seen BE and Pseudomonas as bad as mine in his CF
patients. But it was negative.>

possibly you received

Ambry Genetics Announces 508 FIRST® Cystic Fibrosis Test $59 Assay Detects the Most Common Cystic Fibrosis Mutation

Samples from patients that prove negative for DeltaF508 will be automatically routed to the Ambry Test: CF AMPLIFIED® for the most comprehensive analysis available. With a detection rate of approximately 99%, no other test can identify more mutations than the Ambry Test: CF AMPLIFIED.

What is BE? possibly bronchietasis

Pseudomonas is a genus of bacteria, with Pseudomonas aeruginosa being the most notable species that can cause infections in humans, particularly in those with weakened immune systems. These bacteria are commonly found in the environment, such as in soil and water, and can lead to various infections, including
pneumonia and urinary tract infections.

Pseudomonas seems similar to Mycobacterium avium complex (MAC).

What is your treatment for BE and Pseudomonas?

Cystic Fibrosis Foundation

Some genetic diseases, such as cystic fibrosis, are caused by mutations in a single gene. A gene contains DNA letters that spell out the instructions to make a specific protein. When the protein isn't made correctly, it can lead to a cascade of problems.

There are five classes of CFTR mutations: protein production, protein processing, gating, conduction, and insufficient protein.

The most common CF mutation, F508del, is primarily considered to be a protein processing mutation.

CFTR modulators address various problems caused by different types of CFTR mutations.

Well now I am confused! My pulmo said he was ordering the genetic test that was the most comprehensive. But it does not sound like it. I will have to ask him about it.

Found this: The "reflex" part of the name refers to a two-stage process:
Initial Screening: The test first screens for the F508del mutation, which is responsible for about 70% of CF cases in the white population.
Reflex to Full Analysis: If the first screen comes back with an uncertain or negative result, the lab automatically "reflexes" to a more comprehensive analysis of the CFTR gene to look for other, rarer mutations.

So perhaps my pulmo felt this was comprehensive enough??