In 1966, a nurse pricked the heel of a newborn baby in an Irish maternity hospital, squeezed four spots of blood onto a card, and posted it to a laboratory in Dublin. It was the first year Ireland screened its babies for anything at all. The condition they were looking for was phenylketonuria, almost always shortened to PKU: an inherited fault in the way the body handles one of the building blocks of protein. Caught in the first days of life and treated with a tightly controlled diet, a baby with PKU grows up with an ordinary brain. Missed, that same baby would have been left with profound, permanent intellectual disability.
Those babies are turning 60 this year.
They are the first people anywhere in Ireland to reach their seventh decade with treated PKU, and they are doing it without a map. The research that follows people with PKU through adulthood thins out in the forties, runs dry somewhere in the fifties, and simply stops before the age most of this group has now reached. One of the women interviewed for the only Irish study of its kind put it plainly when she was asked what lay ahead: “There’s no research, there’s no backup.”
TL;DR
- Ireland began newborn bloodspot screening in 1966 with PKU, so the first screened cohort turns 60 in 2026. Ireland also has one of the highest rates of PKU in Europe, roughly 1 in every 4,500 births.
- Evidence suggests adults with PKU age faster on several measures: more arterial stiffness, higher rates of obesity, diabetes and high blood pressure, lower bone density, more white matter change in the brain and more mood disorders than people without PKU.
- The published evidence genuinely stops short of this cohort. The largest recent bone study ran to age 56.8, a brain-ageing study to 48, and no paper at all pairs PKU in its title with menopause in its abstract.
- PKU is one of 16 conditions on Ireland’s Long-Term Illness Scheme, which is not means tested. Sapropterin has been reimbursed here since July 2019 after the HSE overrode two negative cost-effectiveness verdicts.
- If you or a relative was discharged from a metabolic clinic decades ago, going back is the single highest-value thing to do. Diet-for-life is now the standard, and re-engagement is treated as routine, not as a telling-off.
A heel prick in 1966, and what it started
Ireland’s National Newborn Bloodspot Screening Programme was established in 1966 specifically to find babies with PKU, making this country one of the earliest adopters of newborn screening in the world. The programme has expanded steadily since and now screens for nine rare conditions, including cystic fibrosis, congenital hypothyroidism and classical galactosaemia, with uptake above 99.8% of eligible babies. The National Rare Disease Strategy 2025-2030 recommends expanding it further, and screening for severe combined immunodeficiency and spinal muscular atrophy is being added.
The sample is still taken the same way, from the baby’s heel, between 72 and 120 hours after birth. Most Irish parents know it as the heel prick test. Very few know that the whole apparatus exists because of PKU, or that the programme is old enough to draw a pension.
That longevity creates something unusual. Ireland has a continuously screened and treated PKU population going back six decades, which is a genuinely rare research asset. It has not been used. In 2025, Irish clinicians published a review of clinical and developmental outcomes after 50 years of screening for classical galactosaemia. As of October 2026, no equivalent published review exists for PKU, the condition the programme was built around.
Why Ireland has so much of it
PKU is recessive, meaning a child needs to inherit a faulty copy of the gene from both parents. Carriers are entirely healthy and have no way of knowing. In most of Europe the condition turns up in roughly 1 in 10,000 births. In Ireland it is about 1 in 4,500, one of the highest rates on the continent, a quirk of the Irish gene pool that also shows up in the west of Scotland.
The fault sits in an enzyme called phenylalanine hydroxylase, which normally converts phenylalanine, an amino acid present in all protein-containing food, into something else the body can use. Without it, phenylalanine accumulates in the blood and crosses into the brain, where high concentrations are toxic. The treatment is to restrict natural protein severely and replace it with a phenylalanine-free amino acid supplement, usually a drink or a gel, taken several times a day for life.
In practice this means weighing food. Not occasionally, but at most meals, for decades. A slice of ordinary bread can use up a substantial share of a day’s allowance. Meat, fish, eggs, cheese, nuts and pulses are mostly out. So is aspartame, the sweetener in a great many diet drinks, which is why those cans carry a warning that only makes sense to about one person in several thousand.
The first people to grow old with treated PKU
In 2022, researchers at Munster Technological University published the first substantial account of what living with PKU is actually like for Irish adults. Eleven people took part, aged between 21 and 49, recruited through the PKU Association of Ireland. The study covered diet, relationships, fertility and work, but the theme the authors singled out as least represented anywhere in the existing literature was ageing.
The participants were acutely conscious of their own position. Several of the older ones understood that they were among the first people in Ireland diagnosed after screening began, and that nobody had gone ahead of them. One described it like this: “I’m one of the earlier ones, there are older than me, but there’s not really much research done as to what happens later on in life to PKUers.”
Another, in his forties, described the specific shape of the worry, which is not about diet but about the brain: “At my stage in life, I just feel like there’s not really much research done into the older end of the spectrum. So, I’m kind of blocking that out of my mind. What effect does that have when I’m 60 or 70?”
And on the gap that affects half the cohort and has been studied essentially not at all: “Menopause is around the corner for me, I don’t know what’s going to happen then. There’s no research, there’s no backup.”
It is worth saying clearly that these were not people in poor health. All eleven were in full-time work or education. Several had children. The dominant note in the study was not complaint but a wish to reassure the parents of newly diagnosed babies that a full life is entirely available. The anxiety was specific and narrow: not “will I be well”, but “will anyone be able to tell me what happens next”.
What ageing with PKU appears to look like
The research that does exist points in a reasonably consistent direction, and it is not reassuring enough to ignore.
A narrative review published in 2026 in the American Journal of Medical Genetics pulled this literature together under the heading of accelerated ageing. Adults with PKU show more cardiovascular ageing than adults without it, including arterial stiffness and disordered blood lipids, alongside higher rates of obesity, diabetes and high blood pressure. They tend to have lower bone mineral density, more extensive white matter change visible on brain scans, somewhat poorer performance on cognitive testing, and a higher prevalence of mood disorders, all of this despite being treated. The authors propose oxidative stress as the common mechanism, with knock-on mitochondrial dysfunction and DNA damage.
Bone is the single most-studied part of this. A 2024 systematic review of somatic conditions in adults with PKU extracted 51 studies covering 12,602 people, and bone problems were the most frequently reported outcome by a wide margin. Of 38 studies comparing adults on a phenylalanine-restricted diet against healthy controls, 37 found a higher burden of at least one condition in the PKU group. That review was funded by BioMarin, which manufactures two PKU treatments, so it is worth weighing accordingly, though the direction of the finding is echoed elsewhere.
The size of the bone effect matters as much as its existence. A meta-analysis of 4,097 individuals across 10 studies found bone density significantly below age-matched reference values at the lumbar spine and femoral neck, but still within the normal range for age. A 2026 study of 117 people found at least one markedly low score in 10% of adults, against the 2.3% you would expect by chance. The honest summary is that bone density in PKU runs lower than it should, by an amount that is real but modest, and that this becomes more consequential as everyone’s bones thin with age anyway. Our guide to preventing osteoporosis after 50 applies here with extra force.
On the brain, the findings are gentler than the fear. A 2026 study estimated “brain age” from MRI scans in 30 adults with early-treated classical PKU against 59 matched controls. Of eight separate brain-age estimates, only one region showed a statistically robust difference after proper correction. Signals linking brain ageing to historical phenylalanine levels and to white matter damage were present but did not survive the strictest statistical test. This is a long way from the dementia risk that participants in the Irish study were quietly dreading, and it is reasonable to say so.
Where the evidence stops
Here is the part that justifies the worry. Look at the ages in those studies. The bone study of 117 people ran from 6.2 years to 56.8. The brain-ageing study ran from 19 to 48. A 2025 bone study ran to 51.6. The Irish lived-experience study topped out at 49.
Nobody has published on PKU in the seventh decade because, until very recently, there was almost nobody in it. The treated population is only as old as the screening programme that found them, and Ireland’s programme is sixty. The literature is not neglecting older adults with PKU out of indifference; the cohort has only just arrived.
The menopause gap is the starkest illustration. Searching Europe PMC in October 2026 for papers with phenylketonuria in the title and any form of the word menopause in the abstract returns nothing at all. Given that oestrogen loss is the main driver of bone loss in women after midlife, and that lower bone density is the best-documented physical finding in adult PKU, the absence of a single dedicated paper on how those two things interact is remarkable. The woman quoted above was not being pessimistic. She was being accurate.
What you are entitled to in Ireland
PKU is one of the 16 conditions listed under the Long-Term Illness Scheme, which supplies medicines and appliances for that condition free of charge, with no means test and no prescription charges. You need to be ordinarily resident in Ireland. Application forms come from your local primary care centre, or by phoning 0818 22 44 78. We have written separately about how the scheme works and the odd fact that its list has not changed since 1975, which is worth reading if you have never applied.
On medicines, Ireland’s record is better than the paperwork suggests. Sapropterin, sold as Kuvan, helps a minority of people with PKU whose residual enzyme activity responds to it, allowing more natural protein in the diet. The National Centre for Pharmacoeconomics assessed it and recommended against reimbursement in 2009, then assessed it again and recommended against it a second time in September 2017. The HSE approved reimbursement anyway in July 2019, following confidential price negotiations. It is a useful reminder that an NCPE recommendation is advice, and the final call sits with the HSE under the Health (Pricing and Supply of Medical Goods) Act 2013.
Pegvaliase, sold as Palynziq, is an injected enzyme therapy licensed for people aged 16 and over whose blood phenylalanine stays above 600 micromol per litre despite everything else. The NCPE completed its assessment in September 2022 and recommended it be considered for reimbursement if its cost-effectiveness could be improved. If this is relevant to you, ask your metabolic team directly what the current access position is rather than relying on anything written online, including this.
If you left the clinic years ago
This is the most actionable thing in the article. In the early decades of screening, in Ireland and elsewhere, it was common practice to relax or stop the diet in childhood and discharge the patient. The thinking at the time was that the brain was finished developing and the danger had passed. That thinking has been reversed. Current European guidance, revised in 2025, treats PKU as a lifelong condition requiring lifelong control.
Which means a cohort of Irish adults now in their fifties and sixties were told, in good faith, something that is no longer considered correct, and many of them have not seen a metabolic team since secondary school.
Research on getting those people back is sobering. One specialist centre identified 53 adults who had been away from clinic for five years or more, some for over fifty. They managed to make contact with 27. Sixteen completed an educational session. Five actually returned to clinic. The reasons people gave for staying away were mundane rather than dramatic: they had been formally discharged as children and assumed that was that.
If that is you, or your brother, or your wife, the route back is a GP referral to the National Centre for Inherited Metabolic Disorders. There is no deadline that has passed and nothing to apologise for. The advice changed; you were not told. Re-engaging gets you a phenylalanine level, a bone scan if indicated, dietetic input, and an answer about whether you are one of the people sapropterin might help, which was not even a question when you were discharged.
A practical checklist after 50
- Get a current phenylalanine level. Everything else follows from knowing where you actually are, and many people who have been away from clinic for years have no idea.
- Ask about a DXA bone scan. Lower bone density is the best-established physical finding in adult PKU, and it compounds with age-related bone loss. Women approaching or past menopause should push on this specifically.
- Treat cardiovascular risk as a live issue. Blood pressure, lipids, weight and glucose deserve the same attention as the diet, given what the accelerated-ageing literature shows. These are also the parts you can actually change.
- Do not stop the amino acid supplement because it feels pointless. It is the source of most of your protein, and the micronutrients bundled into it. Stopping it while keeping the low-protein diet is the worst of both arrangements.
- Mention PKU to every clinician you see. Many Irish GPs have never had an adult patient with PKU and will not think of it. It is relevant to prescribing, to anaesthesia and to any dietary advice you are given for an unrelated condition.
- If you are a woman who might still become pregnant, get advice before conceiving, not after. High maternal phenylalanine harms a developing baby even when the baby does not have PKU, and control needs to be tight before conception.
- Find the community. The PKU Association of Ireland is the main source of practical information, advocacy and contact with people in the same position, and it was the gateway for the Irish research described above.
For families, and for GPs
If someone in your family has PKU and is now in their fifties or sixties, the useful question is not “are you sticking to the diet”. It is “when did you last see the metabolic team”. Those are different questions and only the second one has an answer anybody can act on.
For clinicians, the pattern worth holding onto is the one Ireland keeps repeating with conditions that were once paediatric and are now lifelong. We built excellent services for children, those children became adults, and the adult provision lagged. We described exactly this dynamic in the context of spina bifida after 40. PKU is the oldest instance of it in the country, because PKU is where Irish screening started.
At Críonna Health we keep returning to the groups whose later years nobody planned for, because that is usually where the avoidable harm sits. Sixty years ago, Ireland decided to find these babies. The logical next step is to find out how they are getting on.
This article is for general information and is not medical advice. If you have PKU, or care for someone who does, discuss any changes to diet, supplements or medication with your metabolic team or GP before acting on them.
📷 Photo by Piret Ilver on Unsplash
