Trypsin testing (Medical)

[Windows]

I’m curious if any of you have ever had your trypsin levels tested? Just wondering how routine it is in the UK. If it’s not routine, you might have been tested if you had a lung or liver complaint.

I’m particularly interested if you have COPD, lung cancer, or liver disease and you have not had trypsin tests.

I’m wondering, if you are a woodworker with COPD, whether the medics ascribe your condition to your profession and skip looking for other factors or whether they look at other causes.

I have a genetic condition called alpha-1 anti trypsin deficiency (A1AT deficiency or AATD). This condition plays a part in both lung and liver disease. Understanding of this condition is still growing but even current knowledge is not as widespread in the NHS as it could be.

Some medical professionals consider A1AT deficiency to be rare (although maybe 1 in 3000 have this condition in the UK), but the potential impacts are much wider with 1 in 30 people in the UK carrying a faulty copy of the gene.

Anyone aware of this already?

Anyway, my practical advice is if you have (or know someone who has) a serious lung or liver problem (pneumothorax, COPD, lung cancer, jaundice, hepatitis, liver failure) or tests indicating a problem (liver function tests, lung capacity tests), make sure you also get your trypsin levels checked.

And if you or someone you know has AATD, make sure that the whole family gets tested and understands the implications. My brother died in his 40s. He might still be alive if we had all understood a little more about alpha-1 anti trypsin deficiency.

 

[StevieB]

Disclaimer - I am a geneticist, not a clinician. I am not giving clinical advice here and anyone who has concerns should speak to a healthcare professional.

Trypsin testing would not be routine, it is only undertaken if there is a clinical reason to do so. Usually that is poor lung function / suspicion of lung or liver disease and would be one of a battery of diagnostic tests undertaken to form a clinical diagnosis. If functional levels are low then a genotypic test would be undertaken (also from a blood sample generally) to confirm whether there is a genetic cause. AATD is a recessive condition, so while you are correct 1 in 30 people may carry a mutant gene, this has no effect on them and it is quite harmless. It is only when an individual carries 2 copies (the 1 in 3000 figure) that a clinical phenotype becomes manifest. There is no 'cure' just as there is no cure for many many genetic diseases (the mutation will be in every cell of your body) but there are lifestyle factors that you can alter to better cope with the phenotypic effects of the condition - these are mostly the usual eat well, don't drink, protect your airways from particles/pollution etc.

While I never advocate 'diagnosis by google' there are some good sites to give general overviews of well understood conditions that can be of use, such as this: https://medlineplus.gov/lab-tests/alpha-1-antitrypsin-testing/ but again, any specific or clinical questions should really be directed to a GP or healthcare professional if you want specific advice or guidance.

 

[Windows]

Thanks for providing that additional detail Stevie.

While it is true that one’s level of concern should not be as high if you have only 1 mutation, I don’t believe “no effect” and “quite harmless” match the current medical understanding. For example, see this paragraph in the article you linked:

“

• If you have one mutated copy of the gene, you are a carrier of AAT deficiency. In these cases, this means you are at slightly higher risk of developing lung disease, especially if you other risk factors, such as being a smoker. You could pass the mutated gene on to your children.

“

Part of the problem in both understanding and describing AATD is that it was first understood as a kind of binary condition (you were either extremely deficient or not) evidenced primarily by pretty extreme effects in young people, but now seems to be an encompassing term for a number of different mutations in the SERPINA1 gene and a recognition that there’s a continuum of deficient levels and effects.

When I was first diagnosed in the 90s, it was because I had a spontaneous pneumothorax. The practical understanding of spontaneous pneumothorax at that time as evidenced by doctors I interacted with personally was that they had no idea what caused it and the best they could say was that it primarily affected tall thin young men. I was tested because I had a cousin involved in medical research in the United States who suggested it. Even once confirmed, doctors didn’t understand the implications. It is now accepted that AATD is a risk factor for spontaneous pneumothorax.

In the early 2000s, the doctors I interacted with understood that AATD was a cause of lung problems, but not as much attention was given to the liver. Now it’s recognised that it’s important to monitor both liver and lung function.

The point being that genetic and clinical research is revealing new information about AATD and SERPINA1 all the time.

Today you may find doctors who know something about it and would advise avoiding smoking to protect your lungs and not drinking alcohol to protect your liver, but fewer that see that the biological mechanisms also suggest avoiding smoke and dusty environments to protect the liver.

 

[StevieB]

As with many situations such as this, the devil will be in the detail. Define 'slightly higher risk' for example. Apologies if my use of the word 'harmless' was poorly phrased, but what that term means genetically is that you are not going to be on any form of screening programme or enhanced monitoring as a carrier, whereas you may be if you carry 2 copies of the gene. The same is true of e.g. cystic fibrosis - 1 in 50 are carriers and never know it or tested for it, but the consequences are devastating if you carry 2 copies of the gene mutation. Once an individual knows they are a carrier, they may then wish to explore personal risk and lifestyle changes as a consequence.

In terms of passing on the mutated gene to your children, if you are a carrier of a recessive gene then yes, you have a 50% chance of passing the gene on to each of your children and these are independent events (unless you have identical twins) so if you have 2 children, there is a 25% chance neither have the gene, 50% that one of them does, and a 25% chance that both do.

I would agree that recent advances in genetics have led to a far greater understanding of the causes of disease and biological mechanisms, but we have yet to really translate that into patient benefit in terms of treatment, but we are learning all the time.

 

[Windows]

Yeah, sadly you’d have to read the literature to get a good understanding of what slightly higher risk means.

When the NHS or MedlinePlus has public, health-consumer content that mentions increased risk, I’d suggest that they consider the risk to be significant enough that they think that the general public should be aware, so we’re talking about risks that are meaningful to individuals.

I get what you’re saying about cystic fibrosis, but AATD is autosomal codominant (not recessive). I believe that this view of AATD has changed over time, so you may see out of date information on this. AATD variants are usually described in terms of the phenotype with two letters. Each letter corresponding to the inheritance from one parent. M is fully functional. Z is one of the defective variants. Someone who is MZ, for example, has one good copy and one defective, but they have negative health effects that are far from academic.

 

[Lons]

I'm not qualified to give opinions on any medical subject, I have a number of family members I can ask if I want to know anything and while I like to be informed my general attitude is that I don't worry about anything until there's something to worry about.

So my uninformed opinion is that we increase our risk to all kinds of nasty stuff every time we interact with others, eat something unless cooked by ourselves or take medication of almost any kind as they all have "risk".
My attitude therefore is be aware, take action to mitigate if possible, make the decision to go ahead with something based on benefit v risk and just get on with life as best we can as it's too bl**dy short.

Edit
I found this interesting to read some time ago. https://www.rcog.org.uk/media/sxup5q24/pi-understanding-risk.pdf