The hill at the end of the walk is where it shows up first. Not the flat stretch along the coast, the last rise, where the path tilts and the conversation stops. Someone who has walked that path for thirty years ends up at the fence halfway up, waiting for their chest to catch up with the rest of them. And the explanation arrives before anyone has asked a question. You are sixty-four. What do you expect.
Sometimes that is the whole answer. Lungs do stiffen a little with the decades, and breathlessness on a climb is not automatically a disease. But there is a version of this that has a name, a cause, a blood test, and a free national programme in Ireland that has been running since 2004. The uncomfortable part is that the people least likely to be offered that test are the people over sixty.
TL;DR
- Alpha-1 antitrypsin deficiency leaves the lungs under-protected and the liver holding misfolded protein. Ireland has some of the highest rates of the Z and S variants in the world.
- About 1 in 25 people here carry one copy of the Z variant: roughly 223,000 people, some 77,000 of them aged 50 or over, plus an estimated 2,600 with the severe ZZ form.
- Ireland runs what the Alpha-1 Foundation Ireland calls the world’s only national detection programme for Alpha-1: over 24,000 people tested since 2004, about 6,000 found to have severe or moderate deficiency. The blood test is free and your GP can arrange it.
- Testing skews young. In the European EARCO registry, 18.2% of people with Alpha-1 and COPD were not diagnosed until 65 or over, and almost 40% of that group had never smoked.
- The HSE’s page on the condition has a section headed “Diagnosing AAT deficiency” that names no test, does not say it is free, and never mentions the programme.
- Section 42 of the Disability Act 2005 bars genetic test results from being processed for insurance, pensions or a mortgage, and since 2018 breaching it carries a fine of up to €100,000 on indictment.
What alpha-1 antitrypsin actually does
Alpha-1 antitrypsin is a protein made mainly in the liver and sent into the bloodstream to protect the lungs. Its job is to restrain neutrophil elastase, an enzyme your immune cells release during infection, which is useful aimed at bacteria and unhelpful when it starts digesting lung tissue instead. Alpha-1 antitrypsin is the brake.
The most common fault, the Z variant, is a single change in the SERPINA1 gene. The protein it produces misfolds, so much of it never leaves the liver, which creates two problems at opposite ends of the body: too little brake in the lungs, and misfolded protein piling up inside liver cells. Someone with two Z copies, written ZZ, has the severe form. Someone with one Z copy and one normal M copy is MZ, which used to be dismissed as carrier status and no longer is.
Ireland’s numbers, and why they are unusual
The foundational work here is Irish. In 2011 a team at the Royal College of Surgeons in Ireland, based at Beaumont Hospital, published the first proper prevalence study for the country in Respiratory Research, combining the national programme’s results with a random sample of 1,100 people drawn from the electoral register. They found Z and S variant frequencies among the highest in the world.
Applying those published frequencies to the Central Statistics Office’s April 2026 population of 5,525,578 gives the scale. Around 2,600 people in the Republic have the severe ZZ form and around 13,000 the intermediate SZ combination. Around 223,000 carry a single Z copy, roughly 111,000 of them over 40 and roughly 77,000 over 50.
What Ireland did with those numbers is genuinely unusual. A targeted detection programme began in 2004 with government funding and still runs out of the RCSI Education and Research Centre at Beaumont. The Alpha-1 Foundation Ireland describes it as the only national screening programme for Alpha-1 anywhere in the world, and the results support the effort: more than 24,000 people tested since 2004, about 6,000 of them found to have severe or moderate deficiency. Globally, fewer than one in ten people with the ZZ form have ever been identified. On the island of Ireland the figure is around 16%. Better, and still a long way from good. Of an estimated 3,000 people with severe deficiency, roughly 2,500 do not know.
The age trap
Alpha-1 has a reputation as a young person’s condition: early-onset emphysema in someone in their forties, a dramatic family history, a textbook case. That reputation is doing real harm to older adults, and the registry data shows how. The European Alpha-1 Research Collaboration (EARCO) analysed 1,565 people who had both Alpha-1 and COPD, registered between February 2020 and October 2024, and sorted them by the age at which the Alpha-1 was finally picked up. Nearly one in five, 18.2%, were not diagnosed until they were 65 or older. That older group looked different from the textbook. Only 47.1% had the severe ZZ form, compared with 78.5% of those diagnosed under 45; the rest had the milder SZ and SS combinations that take longer to declare themselves. And 39.5% of them had never smoked at all, against 15.3% of the under-45s.
That is the heart of it. The people diagnosed late are disproportionately the ones with no smoking history to blame it on. Their breathlessness had no obvious culprit, so it was filed under age.
Meanwhile the testing itself runs the wrong way. Analyses cited by the EARCO team found that being under 55 made a COPD patient more than twice as likely to be tested, and UK data found testing least frequent of all in people aged 65 and over. Guidelines say every person with COPD should be tested once, regardless of age or smoking history. In practice, the older you are, the less likely anyone is to ask.
The same pattern shows up in treatment. In the EARCO data, 43% of those diagnosed under 45 were receiving augmentation therapy, against 24% of those diagnosed at 65 or over. The authors offered the obvious clinical explanation, that the older group had milder disease, and then added a sentence worth quoting: “bias favoring the treatment of younger patients may be a consideration.” Coming from a registry paper, that is about as pointed as it gets.
The HSE page with no test on it
Ireland’s health service does have a page for this. There are 478 conditions in the HSE’s Health A to Z and Alpha-1 antitrypsin deficiency is one of them, which already puts it ahead of several things we have written about here. The page is accurate: the protein is made by the liver, the symptoms resemble COPD, 1 in 25 people in Ireland carry the gene, and you can ask your GP to refer you to the National Centre of Expertise at Beaumont Hospital.
It also has a section headed “Diagnosing AAT deficiency.” That section runs to three sentences. It says the condition is genetic, that several family members may be affected, that many people do not know they have it, and that early diagnosis helps. It does not say what the test is, or that it is a blood test your GP can arrange, or that it is free, and it never mentions the national detection programme. The Beaumont referral appears further down, under “Living with AAT deficiency,” which is to say after you already have the answer.
So the country that built the world’s only national detection programme for this condition has a public health page about the condition that tells you where to go once you know, and nothing at all about how to find out.
What the test actually is
There are two parts to it, and the distinction matters. The first is an alpha-1 antitrypsin level, which measures how much of the protein is circulating in your blood. The second, and more informative, is an AAT phenotype, which identifies which version of the protein you are making. The Alpha-1 Foundation Ireland is explicit that a level on its own is not a diagnosis, because alpha-1 antitrypsin is an acute-phase protein: it rises when you are unwell. A level drawn during a chest infection, or in the weeks after one, can come back reassuringly normal in someone who is in fact deficient. If you have a family history, ask for both by name.
Both are free through the HSE-funded programme and both can be arranged by your GP. Following WHO, American Thoracic Society and European Respiratory Society guidance, testing is recommended for everyone with COPD regardless of age or smoking history, severe asthma that does not respond to usual treatment, liver disease of unknown cause, the skin condition panniculitis, vasculitis, a low AAT level, and all first-degree relatives of someone already diagnosed.
Alpha-1 Foundation Ireland is at the RCSI Education and Research Centre, Beaumont Hospital, Dublin 9. You can reach them on 01 809 3871 or 01 809 3749, or at alpha1@rcsi.ie. There is a dedicated Alpha-1 clinic at Beaumont on Wednesday afternoons. For a condition in which the typical person reportedly sees up to five doctors across seven years before anyone names it, that is a short enough route.
If you are “only a carrier”
This is the part that matters to the largest number of readers, and it deserves stating carefully rather than dramatically. Irish researchers ran a family study designed to answer it honestly, recruiting through families rather than clinics and excluding the relative whose diagnosis triggered the referral. The final analysis compared 89 people with MZ against 99 of their own MM siblings, which controls for a great deal that ordinary studies cannot.
The result was clean. MZ siblings who had never smoked had essentially the same lung function as MM siblings who had never smoked. MZ siblings who had smoked had worse lung function than MM siblings who had smoked, and the gap widened in those with more than 20 pack-years. A follow-up Irish study of 44 families found the same shape for the SZ combination: no excess risk in never-smokers, clear excess risk once smoking entered the picture. There are an estimated 40,000 people in Ireland who are both MZ and smokers.
So carrying one copy is not a diagnosis and not a sentence. It is a multiplier, and smoke is what it multiplies. The practical reading is almost cheering: for a carrier, stopping is worth more than it is for most people. Irish cessation programmes for people with severe and moderate deficiency report a clear positive effect on quit rates.
The liver half nobody mentions
The lung story is the famous one. The liver story arrives after 50, and it is where carrier status stops being academic.
An international workshop report published in April 2026, with the RCSI team among its authors, pulled the evidence together. In the UK Biobank, people with MZ had slightly raised liver enzymes and moderately increased odds of liver fibrosis or cirrhosis. Roughly 10% of liver transplant recipients of European descent carry MZ. The protein deposits inside liver cells accumulate with age in carriers, and the more fibrosis present the more deposits, which suggests a loop rather than a straight line. Carriers who do develop cirrhosis deteriorate faster than non-carriers.
Now look at the list of things that turn a carrier’s modest risk into a real one: male sex, age of 50 or over, a BMI of 30 or more, diabetes, and alcohol. Nothing exotic there, and three of the five are things we can actually do something about. The honest summary from the workshop is that most carriers never develop clinically significant liver disease, but that they are sensitive to additional hits. If you know you are MZ, the weight, the drink and the blood sugar stop being general advice and start being specific advice.
The treatment question Ireland answered in January
For severe deficiency there is one specific drug: augmentation therapy, a weekly infusion of pooled human alpha-1 antitrypsin topping up what the liver is not supplying. It does not reverse damage, though registry evidence associates it with improved survival.
Ireland has now assessed it. The National Centre for Pharmacoeconomics commissioned a rapid review of alpha-1 proteinase inhibitor (Prolastin) on 19 December 2025 and completed it on 13 January 2026. The outcome: a full health technology assessment is not recommended, and on current evidence the NCPE considers that it should not be reimbursed. The NCPE advises; the final call rests with the HSE under the Health (Pricing and Supply of Medical Goods) Act 2013. It is the only assessment of any Alpha-1 augmentation product on the NCPE’s books.
There is an awkward symmetry in running the world’s only programme to find people with a condition and then declining to fund the one drug aimed at it. A diagnosis is still worth having. It changes what you are told about second-hand smoke, occupational dusts and fumes, and which vaccines matter. It gets you pulmonary rehabilitation and a respiratory service rather than a repeat inhaler prescription. It puts your liver under surveillance. And it tells your brothers, sisters and children that a free blood test is worth an afternoon.
The law that stops the test being used against you
The most common reason people give for not getting tested is not fear of the result. It is fear of what the result will do to a mortgage application or a life assurance premium. In Ireland that fear has a statutory answer, older and sharper than most people realise.
Section 42 of the Disability Act 2005 came into force on 31 December 2005. It prohibits the processing of genetic data in relation to five things by name: a policy of insurance or life assurance, a policy of health insurance or health-related insurance, an occupational pension, retirement annuity or other pension arrangement, the mortgaging of property, and employment. Since 25 May 2018, when the Data Protection Act 2018 rewrote the penalty, breaching it is an offence carrying a class A fine on summary conviction or a fine of up to €100,000 on conviction on indictment, and a court may order the data destroyed.
Two caveats, because precision is kinder than reassurance. The Act defines genetic testing as the analysis of DNA or RNA, which squarely covers the genotype result telling you whether you are MZ or ZZ, and explicitly includes testing to identify the carrier of a disease; a serum protein level is a different kind of measurement. And none of this stops an insurer asking about an illness you have actually been diagnosed with. What section 42 blocks is the use of the genetic result itself. Section 43, which dealt separately with family history, was repealed on the same day in 2018.
Five things to do this week
- If you have COPD, emphysema or chronic bronchitis and have never been tested, ask your GP for an AAT level and an AAT phenotype. Say both names. Your age and smoking history are not reasons to skip it.
- If a parent, sibling or child has been diagnosed, get tested whether or not you have symptoms. First-degree relatives are explicitly covered by the free programme.
- If a level was done during or just after a chest infection and called normal, ask whether a phenotype was ever run.
- If you carry one copy and still smoke, treat quitting as the highest-value item on your health list this year, and ask about HSE support.
- If you carry one copy and are over 50, ask at your next review about liver function tests, and have the honest conversation about weight, alcohol and blood sugar.
When not to wait
Contact your GP or out-of-hours service promptly if breathlessness is worsening week on week rather than year on year, if chest infections are arriving more often or taking longer to clear, or if you notice yellowing of the skin or eyes, swelling of the legs or abdomen, or unexplained weight loss. Sudden severe breathlessness at rest, or coughing up a significant amount of blood, is an emergency: call 999 or 112.
The point of knowing
Ireland has done something here that no other country has done, and then half-told its citizens about it. The programme exists, the test is free, the phone is answered in Beaumont, and the law has protected the result for two decades. What is missing is the short sentence connecting them. The hill at the end of the walk may well just be the years, but it costs one blood test to find out whether it is something with a name, and in Ireland that test has been paid for since 2004.
At Críonna Health we write about ageing well in Ireland, including the services and entitlements that exist but are rarely signposted. Nothing here replaces advice from your GP or respiratory team.
📷 Photo by Anna Hunko on Unsplash
