My daughter was dx with a positive sweat test by our Lung Center (Buffalo, NY). After a 15 year diagnosis they retracted it saying that after identifying her mutation (Variance 7542) she does not have CF. She has a positive sweat test with no lung involvement. They were pretty fascinated with all of this and wanted to continue to follow her but we chose not to return, as she is pretty healthy. She also has Down Syndrome, which may effect the sweat test also.
Normally, I would question why they would retract it if the sweat test is positive because that is gold standard, but seeing that Down's can affect the sweat test and they have identified the mutation (I'm assuming they have down a full screen for all mutations/deletions etc., the retraction does make sense. It probably is very rare as there are few other conditions that can alter the sweat test in the same away, and from my friends who have children with Down's, I under that failure to thrive is a challenge they face too, so the doctors would originally put it down to CF (with the high sweat test). All that said, I'm thinking it would make sense to at least annually have her checked out by the CF center since my understanding is they are constantly finding more and more mutations.
Usually the state of the patient's health issues like failure to thrive, thick mucus with constant lung and ENT (Ear, Nose and Throat) infections AND a positive sweat test are adequate for a CF diagnosis. A positive sweat test and the results of genetic testing aren't sufficient on their own, there needs to be CF type health issues plus one or the other tests to call it CF. Many severe forms of CF have marginal sweat tests while many GI dominant presentations tend to show up at the high end of a sweat chloride test. A person can be unquestionably CF from genetic testing and show no symptoms and a sibling with identical mutations is ravaged by CF.
I've been on the receiving end of late CF diagnosis that was reversed and reversed again. I went from not the slightest idea I had anything akin to CF to a diagnosis of record pancreatitis and two positive sweat tests. The diagnosis of CF was based on my pancreatic cystic fibrosis, a chest CT showing a lot of old scarring and the terrible state of my health at the time.
After genetic testing I was informed I don't have CF, just a carrier. I felt that the definition of CF was on shakey ground genetically speaking. And I speak genetics. As a cyto-geneticist one thing about mammalian genetics is how freakishly rare a true mono-genetic disease like CF is. A disease or any genetic condition like blue eyes or the hue of one's skin has many genes at play, not just a single gene making you fair skinned or some other physical feature inherited from mom or dad. CF wasn't chosen for the suffering few that desperately need a cure, CF seemed to be the perfect single gene disorder to use for research. The hope of a cure undoubtedly drove the front line researchers but almost every genetic disease is influenced by several other genes. Increasing CF from one gene to two genes would have made for an impossibly complicated disorder to work out. We didn't count on 3000 mutations of the CFTR (Cystic Fibrosis Transmembrane electrolyte conductance Regulator) gene. There are a few CF like genes that are known but specifically cause pancreatic CF and all the GI fun that goes with it. An example is Spink 1, and it is usually part of the CF screening when a complete genetic test for CF is run.
The genetic definition of CF is a moving target. I don't know why some new diagnoses involve patients who fit the current genetic definition of CF but are classified as CRMS (Cystic fibrosis Related Metabolic Syndrome). I have seen a number of posts by people wondering why they were pigeon holed in one spot over another. Even some of the approved CF centers seem to be way out of touch when it comes down to a CF diagnosis. If any doctor is critical to a CF center it is a pulmonologist. When they specialize in CF, they tend to keep their pulmonary knowledge most current. Cystic Fibrosis was first named after the type of scarring showing up in the pancreas of patients. A child born in 1950 with pulmonary CF had a lifetime measured in hours. Only milder cases, those with less pulmonary issues lived long enough to be diagnosed. Hence CF was characterized by the type of scarring or fibrosing of the pancreas, not the lungs. Today we know it affects one or both plus every wet membrane on or in our bodies is a potential victim. I have experienced a definite bias when I see a CF specialist known for his/her prowess in treating pulmonary CF. CF was incorrectly considered a pancreatic/GI disease long before it was incorrectly considered just a pulmonary disease with some GI dysfunction. It can be either GI or pulmonary dominant or both.
For most of the time since 1989 when the CFTR gene mutation was established as an autosomal recessive genetic disorder, CF was defined by a patient with two identical CFTR mutations known to cause CF. You could have T polymorphisms or TG's coming out of your ears and it was disregarded as having no effect on the disease. Two different mutations, one on each chromosome wasn't part of the definition and having one chromosome clean of a mutation regardless of the other mutation's effect made you an asymptomatic carrier.
What? Ok, CF is a recessive gene which means by itself it will not cause CF, there must be the same gene from both parents. Autosomal just means any of your body cells excepting sperm and eggs. The reason I mention polymorphisms which in genetics means a repeated base or base pair like a key stuck on a typewriter. This type of error can interfere with the function of the gene, in effect like having a ladder with a gap because 7 ladder rungs have been compressed, causing too large of a gap to step past.
The reality of CF still comes down to the health issues. Doctors can better treat a patient that has an accurate diagnosis. As silly as that comment sounds, I spent fifty years being treated for CF issues that appeared to my many doctors as separate and unrelated. What I see happening is a variation of the blind men trying to describe an elephant. The guy feeling the tail imagines a rope or whip, the guy at a leg feels a tree and so forth.
It seems I am always on the verge of anger when I sense a CF specialist is not working from the current play book. They have my sympathy up to a point. The moving target of CF genetics requires more than a casual understanding of genetics. Most doctors' understanding of medical genetics is limited to gross genetic diseases like Down's Syndrome, Klinefelter's syndrome or Fragile X.
The idea that CF is an autosomal recessive disorder requiring two identical known-to-cause-CF mutations, is OBSOLETE. It remains true but the combination of two known disease causing mutations, one on each chromosome, is also true. Somewhere around a million to possibly 7 or 8 million mutation combinations could cause CF is also true. It turns out that not all single mutations are harmless. The classic definition of a carrier, having only one CFTR gene mutation is also considered to be asymptomatic. Many carriers have mild symptoms, some actually develop CF or are born with it fully expressed and penetrating to the pancreas and potentially the pulmonary system. The definition of CF shouldn't be discounted because a patient's genetics doesn't fit the strict definition of CF.
If your daughter doesn't have CF issues, I would like to congratulate you and her. If she has pancreatic or GI issues and not lung issues, I'd look for a pancreatic specialist and maybe seek a CRMS diagnosis. Down's children tend to be salty, I've kissed more than my share of them and I remember noting that quality to their skin. Little kids with Down's, in my experience, are very affectionate and love affection. They seem to have more than average ENT problems and that can cascade if a lot of mucus is aspirated or swallowed.
Are you satisfied with their decision to change her diagnosis?
LL...can I pull a stand from your great info and ask if you have a theory on why gi issues have higher sweat tests and whether there are any studies on that....I was literally today theorizing that ds has so many gi issue as well as severe aquagenetic wrinkling for the same reason he sweat test was so high (133). I don't know how they all relate, but my gut was they do....and I similarly think it relates to why the vertex combo helps lung function but has such a small impact on sweat levels....
Thank you for your very in depth post. A lot of it was over my head but I believe I get the gist. Her first two years were very tough with many hospitalizations for pneumonia and croup. Her breathing was always labored. GI was an issue but not a huge one. After a pneumonia that basically traveled from lobe to lobe, she was sweat tested with positive results. This was in 1994. My other children were tested. My son, who has had more pneumonias, infections than I can count was a negative sweat test, as was my oldest who barely had a cold her entire childhood (who has since been dx with celiac). After some genetic linkage it was determined my son is a carrier. Years later after a stool test was done, we stopped the enzymes due to a normal pancreas. After years of therapies and high fat salt diet (she never had trouble gaining weight and is now overweight) they tell us never mind, she doesn't have CF. We never looked back and never returned saw them again. Occasionally the Dr will call to ask how she is and wants us to bring her in to swab her throat and do a chest X-Ray. She never did get a hang of the PFTs so I never felt those numbers were accurate. I came across this site and was curious to know if there were other stories like ours.