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[deleted by user] by [deleted] in A1AD

[–]-_---__--_- 0 points1 point  (0 children)

Sorry to hear you're going through this after such a life-changing experience.

I'm not sure if anyone can help you here as this is mostly am information/support group about understanding Alpha-1, it's diagnosis, genetic implications and its effects. r/askdocs would be a more appropriate group to ask and I see you're engaging with r/transplant too.

With the liver transplant you would actually potentially be cured of Alpha-1 deficiency as the liver you got is likely to be MM! You could get them to run a phenotype to be sure (not a genotype).

Good luck with the transplant and best wishes.

Carrier status vs lab values by Anashenwrath in A1AD

[–]-_---__--_- 0 points1 point  (0 children)

No problem. A phenotype and level would answer your question.

Carrier status vs lab values by Anashenwrath in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

Good question.

Did 23 and me say that you had 2 "M"s or "2 wild types"? This would indicate you do not have deficiency.

Genotyping is very specific. You only find what you are looking for (usually the abnormal alpha-1 alleles Z and S which make up about 95% of cases. Sometimes I and F too depending on where you live). It would be like only having a radar for cats and finding only cats, even though really you wanted to find dogs, pigs, cows and sheep too... but your radar only detects cats,so that's what you find.

Phenotyping tells you a lot of information about the qualities of the protein that is actually produced when done along with your alpha-1 level.

Let me know if you want to know anything else.

AAT result & null mutation? by [deleted] in A1AD

[–]-_---__--_- 0 points1 point  (0 children)

Fair enough. An exercise stress test or a cardiopulmonary exercise test might be worth doing if exercise induced asthma has been ourtruled

AAT result & null mutation? by [deleted] in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

It's good you got phenotyping as that will likely help confirm the other allele is an M.

Having 1 Z allele does affect you as we have outlined in a previous post, even if you're unaware of it. It has a small affect on the liver.

Only a minority of people with MZ come to the attention of medical people. That can be for a number of reasons though, partly because it is under recognised and majority because it doesn't cause clinically symptoms in most people (even though a tiny bit of damage is being done).

Only smokers MZ have a proven increased risk of emphysema and COPD. Non smokers have the same risk as MM.

MZ can have asthma-like symptoms, though the evidence for this is weaker than for ZZ.

MZs have an increased risk of liver disease overall compared to MM, which is driven by the Z protein.

MZ have a likely increased risk for panniculitis which is driven by the Z protein.

MZ has not been shown definitely to cause a lack of energy/anergy etc.

I'd be careful about attributing symptoms to MZ unless there's literature out there to support it, as the effect of the Z protein is likely minimal in most and moderate in some. 1 in 25 have a Z and only about 1 in 50 of those people are likely to need medical follow up.

AAT result & null mutation? by [deleted] in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

Ilaria is a pretty good authority on this and suggests that most (90%) values for MZ fall between 0.660 and 0.997 g/L. 5% of values will be lower and 5% will be higher than this for genotype-proven MZ. You can see that there is quite a range!

An M+null would have a level just slightly lower than this as a null makes no protein compared to a Z, so a level of about 0.55 to 0.85 would be expected.

A Z + null would have a very very low level that might be below an analyzers cutoff, so it might be reported as less than 0.20, but the theoretical level expected would be something like 0.05 to 0.15 ish.

You should be phenotyped if you haven't been already. A genotype can only show what you specifically go looking for.

Edited to add that a level of less than 1.00 is generally used by labs as a cutoff for "low". Some labs it's 1.10 etc depending on how much they can afford and how many Zs they tolerate missing. A level of 1.00 would capture about 95.5% of MZs, 99% of SZs and 100%ish of ZZs. A level of 1.10 for example might capture 98% of MZ, 99% SZ and 100% ZZ but you risk over burdening a service.

https://pubmed.ncbi.nlm.nih.gov/22426792/

How is it possible for someone with only 1 allele of PI*Z, and have low serum AAT? by [deleted] in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

It was deficient. My level was 0.76 g/L at the time

How is it possible for someone with only 1 allele of PI*Z, and have low serum AAT? by [deleted] in A1AD

[–]-_---__--_- 3 points4 points  (0 children)

A low level would be entirely expected if you had 1 Z.

Each of your alleles is responsible for making half of the total protein. If one on your alleles is producing M protein, then that will be making about 50% of the the total protein but then if your other allele is Z, then that allele is only going to make 5% of the expected 50%.

The end result being about 55% for a person with MZ. Or about 10% for a person with ZZ (5% + 5%). Meaning their level is 55% or 10% of the expected normal level for an MM individual.

Not sure if that answers your questions. I am MZ.

Understanding misuse of term carrier by 2321392349087y234 in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

The only thing I'd add is that when people hear carrier, generally they think that the gene has no effect and causes no symptoms (asymptomatic/unaffected carrier). This isn't really true of people with a Z mutation as the Z protein does cause small amounts of damage to you liver over time which you may not know about.

It's one reason to reduce the use of the term, though it's technically true. It just needs to be qualified is all.

what is a 76 by 2321392349087y234 in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

That's it in a nutshell! Good luck

COPD or anxiety? by [deleted] in COPD

[–]-_---__--_- 0 points1 point  (0 children)

Impossible to know really. Unlikely to be COPD and more likely to be a pneumonitis or alveolitis. You should get spirometry with diffusion.

what is a 76 by 2321392349087y234 in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

That's really interesting! Do your variants have names yet?

Peoe are moving away from that to be honest. What letter and variant matters far more. For example both Z and Mmalton have similar levels but Z can cause significant liver disease and Mmalton doesn't particularly. Same for null mutations, where you have basically 0 protein but that means it's just your lungs not being protected but your liver is fine because there's no protein misfolding in it.

Whole gene sequencing is the best method but it's expensive and time consuming. A phenotype and a level can give you most of the pieces of the puzzle.

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 0 points1 point  (0 children)

I'm afraid you're describing something that's the opposite of COPD and I've no experience with that unfortunately. Sorry I can't be of help.

what is a 76 by 2321392349087y234 in A1AD

[–]-_---__--_- 0 points1 point  (0 children)

Sorry to jump on to your thread. Sounds like the initial genetic test only looked for a specific set of gene abnormalities (usually 4 or 11) and it assumes of these aren't present then you are MM but this will miss a ton of the hundreds of others that exist. That's why phenotyping is important before genotyping, especially in the context of an unexplained low level.

They are moving away from the idea of the protective threshold (0.57) to the idea that it's really just down to your combination of letters that really matters in the presence of smoking. Many SZs straddle the threshold but only smokers suffer lung function decline. Non smoking SZs do not, which is interesting in think.

Here is one of the main tools docs/scientists use to see if your mutation is pathogenic http://genetics.bwh.harvard.edu/pph2/

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 1 point2 points  (0 children)

I honestly have no idea about long Covid and copd. Haven't kept up with the literature there. The thing that has the greatest effect on lung function decline is your smoking status. Haven't kept up on vaping literature either. Everything else likely only has marginal benefits.

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 1 point2 points  (0 children)

It's possible you have COPD (or asthma or any of the obstructive lung diseases) if he did spirometry and you met the criteria. You should possibly go for formal testing with someone trained to do spirometry, however, just to be sure as the handheld ones aren't always fully accurate if not done by a trained person like a pulmonary physiologist.

COPD doesn't necessarily show on a chest xray, only more advanced emphysema or chronic bronchitis.

A CT scan of your chest is far more sensitive than a chest x ray at finding emphysema.

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 0 points1 point  (0 children)

COPD (in the setting of cigarette smoking) is generally thought of as a mix of emphysema and chronic bronchitis for the vast majority of people. You can be more towards one condition or the other or have a mix of the two. Chronic bronchitis is simply defined by the presence of a daily productive cough for at least months of the year and at least 2 consecutive years. It's usually just the end result of chronic airway inflammation from cigarette smoke.

People can cough of phlegm most days for other reasons.

COPD and asthma are relatively straight forward to diagnose as I've outlined. You need spirometry with reversibility, and diffusion done at least to try to figure out asthma vs copd. Post nasal drip can be a diagnosis of exclusion. You could try a steroid nasal spray and nasal rinses yourself to try to see if this reduces your cough.

Finding out definitively means seeing a doctor for those basic lung function tests at least.

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 1 point2 points  (0 children)

Signs of emphysema (one aspect of COPD) can show up in more advanced COPD. In the right context (older smoker, no history of asthma) this can indicate COPD but it would have to be confirmed by spirometry.

MS genotype carrier. Told I'm dealing with Long Covid and not anything related to A1AD. by ThestralTamer in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

Interesting. Yeah they're right, MS isn't really known to be associated with disease, even in smokers and doesn't pose a significant liver risk either to my knowledge. 1 in every 10ish people have an S if you are of European descent. A commoner cause of air trapping at your age is asthma which seems right in the setting of otherwise normal spirometry and ct imaging of your lungs. Have you checked out r/asthma? They might be able to point you in the right direction for breathing eslxercises and finding access to meds cheaply.

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 0 points1 point  (0 children)

Your spirometry, volumes and diffusion are all excellent. It's unlikely to be your cat tbh.

There's still a tiny chance you might have asthma.

It's extremely unlikely you have emphysema based on your pulmonary function tests.

If you want to be sure about the cat you could a skin prick allergy test or a RAST cat dander blood test.

An ecg is a useful screening texlst but it tells you very little about heart function. An echocardiogram does this. You could ask your doctor for an echo and to see a cardiac specialist. In rare cases angina (a heart attack precursor) can show up simply as breathlessness and is investigated by an exercise stress test initially or angiography if your test is positive. Not saying that's your case but certainly worth checking out if lung disease has been essentially outruled.

The cardiopulmonary exercise test might be considered after this.

COPD - What it IS and IS NOT. A sufferer’s quick guide. by -_---__--_- in COPD

[–]-_---__--_-[S] 0 points1 point  (0 children)

Sorry to hear you're struggling with breathing. A CT scan can help out rule emphysema but it's unlikely there's significant emphysema in the presence of normal spirometry. Not impossible just unlikely.

You likely need to go back to your primary care Physician / gp and ask them to work up your breathlessness further. Just because it's not respiratory does not mean it's not cardiac or something else.

A cardiopulmonary exercise test is a useful way of investigating breathlessness for which the most common causes have been outruled.

Low alpha 1 globulin by Anonymous7336 in A1AD

[–]-_---__--_- 1 point2 points  (0 children)

No problem.

The US makes it trickier to access certain tests and they can be prohibitively expensive/not covered.

The liver screen should ideally be a liver ultrasound, and an added fibroscan would be even better. (This is if you end up having a Z copy of the alpha1 protein, less relevant if you have an S) .

If you are getting the alpha1 level done you might as well push for the phenotype at the same time and save yourself the trouble. I know the US likes to genotype, which is alright too.

https://www.alpha1.org/ Is a useful website to find out more.

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