1. Deliver a UK-wide map of rare conditions: The four UK nations must urgently fund comprehensive rare condition registries and work in partnership to map all 7,000 rare conditions. Robust national data infrastructure is not optional, it is the foundation of equitable service planning, resource allocation, and healthcare delivery.
2. Close the evidence gap through fair research investment: Government and research funders must correct the imbalance in research investment by directing funding towards rare conditions. Decision-makers must also reform evidence standards to recognise that uncertainty is an inherent feature of rare conditions and should not be used as a barrier to access or innovation.
3. Mandate system-wide accountability for rare conditions: Healthcare systems must stress-test policies, commissioning decisions, and service delivery frameworks against the realities of low-prevalence conditions. This must include systematic auditing to identify gaps, eliminate inequities, and enforce consistent standards of clinical accountability across all services.
4. Embed rare conditions into mainstream healthcare delivery: Current reforms across the UK healthcare system present an opportunity to fully integrate rare condition care into routine service provision. Failure to act now will entrench existing health inequalities for the 1 in 17 people in the UK that will be affected by a rare condition at some point in their life.
5. Commit to a bold successor to the UK Rare Diseases Framework: UK governments must commit to a long-term successor to the UK Rare Diseases Framework that delivers measurable improvements for people with rare conditions. This successor must set clear targets, and the nations must respond with adequate funding, directly addressing the structural drivers of inequity identified in this report.

Further reading on the hub:

• Top picks: Rare diseases

On 7th July 2025, we were told our daughter was one of around 200 people in the world with an ultra-rare genetic brain condition - DeSanto-Shinawi syndrome (DESSH). I remember the date with uncomfortable clarity.

For months before that conversation, I had reassured myself that everything would be fine. Frankie was slower than other children her age. She was late to crawl. Her words were few. There were subtle developmental differences, but nothing dramatic.

I anchored to what felt safer: she had had meningitis as a baby, and developmental delay could be explained by that. Temporary. Understandable. Reversible.

When bias tries to protect

Even when experienced clinicians gently suggested there might be something more going on, I reframed their concerns in my own mind. I did not dismiss them openly, but internally I diluted their signal.

Looking back, the cognitive biases are obvious. Anchoring bias fixed me to the meningitis explanation. Confirmation bias led me to search for reassuring signs and discount the rest. Optimism bias made the best-case scenario feel like the most probable one. Emotional bias did the rest.

When it is your own child, the mind protects you.

Individually rare, but collectively millions

When the diagnosis came, it felt like a bomb going off in slow motion. The genetics were explained clearly. A change in a single letter of the WAC gene. One functioning copy instead of two. Reduced WAC protein, crucial in early brain development. Lifelong neurodevelopmental consequences.

And then the hardest sentence - there is no medical treatment.

Therapy and support, yes. But no drug to alter the biology. No realistic gene therapy on the horizon. For a condition this rare, commercial drug development is not viable.

For families across the UK, the annual Rare Disease Day shines a light on this reality. Organised nationally by Genetic Alliance UK, it highlights the inequities faced by people with rare conditions: delayed diagnosis, fragmented care, limited research infrastructure and a system not designed for small numbers.

Each condition is individually rare. Collectively, they affect millions.

There are over 7,000 rare diseases. In that context, rarity is not marginal. It is structural.

Multiple barriers to safe care

Rare disease is a diagnostic safety issue, because children are often reassured repeatedly before referral. Developmental differences are attributed to variation. Early signals are softened by probability thinking.

It is an equity issue, because funding and infrastructure follow prevalence and commercial viability. And it is an innovation issue, because rare disease is now reshaping how medicine thinks about treatment.

After Frankie’s diagnosis, I immersed myself in the biology. I read the literature on WAC protein, studied animal models and tried to understand which pathways were disrupted and which might theoretically be adjusted. I connected with the DESSH Foundation and learned from the work of Professor Shinawi and others who had characterised the condition. The gene was known. The pathway was increasingly mapped. What was missing was treatment.

Hope found in AI and existing drugs

Then I came across the story of Matthew Might, a computer scientist whose son had an ultra-rare genetic condition. Rather than accepting that a genetic diagnosis was the end of the road, he treated it as the beginning. Using machine learning and large-scale biomedical data analysis, he interrogated genetic networks and drug databases. His work contributed to the development of the US National Institutes of Health Biomedical Data Translator, an open-source AI platform designed to connect genes, proteins, pathways and existing drugs.

The question shifts from “Can we fix the gene?”—often impossible—to “Can we adjust the biological pathway using a safe, already licensed drug?”

For rare diseases, this reframing is transformative. If a gene reduces the production of a protein, and that protein sits within a measurable pathway, then perhaps an existing medication could nudge that pathway in a favourable direction.

Trialling treatments safely

At Mayo Clinic, scientists including Laura Lambert and Dr Whitney Thompson began exploring whether this computational approach could be applied directly to children with specific rare conditions. In one child with DeSanto-Shinawi syndrome, AI-driven pathway analysis identified a licensed paediatric neurology drug that might plausibly increase WAC protein expression. Before prescribing anything, the team tested the drug in the cells taken from the child. WAC protein levels increased towards normal. It was not proof of cure. It was not certainty. But it was measurable biological change.

After careful discussion and risk–benefit analysis, treatment was started. The developmental progress that followed was described by the child’s family as striking.

It’s one person’s experience. Hope is not evidence. But hope grounded in measurable biology becomes hypothesis, and hypothesis becomes trial.

Raising funds to reduce inequity

The barrier is not plausibility. It is funding. Repurposed drugs are often off-patent.

There is little commercial incentive to fund small, rigorous trials for conditions affecting a few hundred children worldwide. That is why Rare People – The Research Charity I set up was established.

Our mission is to raise funds to support high-quality, properly designed clinical trials of AI-identified repurposed drugs for rare genetic neurodevelopmental conditions. The first funding priority is a formal clinical trial in DeSanto-Shinawi syndrome, with ethics approval in place in the United States and work underway to enable participation from children outside the US, including in the UK.

Rare diseases can shine a light on wider possibilities

Beyond one charity and one condition, something larger is emerging. Rare disease research is demonstrating the practical power of AI in medicine, not as hype but as structured, hypothesis-generating science.

AI can interrogate millions of data points across gene networks and pharmacology, surfacing plausible connections that no individual clinician or researcher could reasonably synthesise alone. Used responsibly, with transparent governance, peer review and rigorous trial methodology, these tools can strengthen rather than threaten patient safety.

Rare diseases are showing us that treatment may become more personalised, pathway-driven and responsive to measurable biological markers. They are challenging us to design systems that do not overlook small populations. They are exposing how cognitive bias operates quietly even in experienced clinicians. And they are demonstrating that when families, scientists and clinicians collaborate across borders, innovation can move faster than traditional commercial pathways allow.

Frankie

Frankie is a joyful, loving little girl. I would not change who she is. But I do want her to have the same opportunities, the same freedom to dream and the same access to scientific ambition as children with common conditions.

Equity in healthcare must include those with the rarest diagnoses.

If we build a system capable of recognising rare disease earlier, mitigating cognitive bias, and harnessing AI safely and ethically, we build a safer system for everyone.

Photo shows Rob holding Frankie, both looking and smiling at the camera

Share your insights

Have you been affected by any of the issues raised in this blog? Do you or a loved one have a rare disease, or perhaps you work with people who do. If you have insights to share around rare diseases and patient safety, you can comment below (sign up first for free) or email the team at content@pslhub.org

1 England Rare Diseases Action Plan 2025

The UK Rare Diseases Framework, published in January 2021, set out a shared vision for addressing health inequalities and improving the lives of people living with rare diseases across the UK. This is the fourth action plan setting out how the Department of Health and Social Care and delivery partners will implement the UK Rare Diseases Framework in England.

2 How one woman’s missed referrals exposed a systemic gap in hereditary cancer care: Why I'm campaigning for Rachel's Rule

When Stuart Ball's wife Rachel passed away in August 2025, she was just 47 years old. Her death was not inevitable. It was the result of years of missed opportunities—signs that were there in plain sight but never joined together. What happened to Rachel should never happen to another family. Stuart shares Rachel's story and tells us why he is campaigning for Rachel's Rule—a call for a system safeguard that ensures hereditary risks are not missed.

3 National Organization for Rare Disorders: Rare Disease Database for patients and families

The National Organization for Rare Disorders (NORD)’s Rare Disease Database provides brief introductions for patients and caregivers to specific rare diseases. 

4 OrphanAnesthesia: Patient Safety Card

OrphanAnesthesia offers a Patient Safety Card for all hospitals, patients, and support groups. The patient or the physician fills in the name of the rare disease to notify the anaesthesiologist/ emergency personnel of the rare disease, and of the recommendation for the anaesthetic management. The card should be given to the anaesthesiologist before anaesthesia. It should be carried by the holder in case of emergency. 

5 Highlighting Loeys-Dietz syndrome and the need for awareness

Loeys-Dietz syndrome (LDS) is a genetic disorder affecting connective tissue, which supports, protects and gives structure to various tissues and organs. This article tells the story of Sharon, a 53-year-old woman from Bristol, who died in December 2022. Her family now advocates for greater awareness of LDS to prevent similar tragedies. Sharon’s death, attributed to natural causes compounded by neglect, highlights systemic failures in promptly recognising and treating her aortic dissection.

6 Rare care matters: The struggle to access diagnosis and care for rare autoimmune rheumatic disease patients

The Rare Autoimmune Rheumatic Disease Alliance (RAIRDA) has launched a report revealing that individuals living with rare autoimmune rheumatic diseases (RAIRDs) experience stark variations in their care and treatment. The report paints a concerning picture: nearly one in three respondents waited more than five years for a diagnosis, with the average wait time standing at two and a half years. 

7 “No one would believe me”: A common feeling for people living with a rare disease

Having a diagnosis can be very important, not only in order to consider medical needs, but sometimes it can also come as proof that something is happening to the body, proof to others that there is something going on. Several people across the globe, with different rare diseases, have shared their story, telling us about needing to be heard and understood.

8 GIRFT - Spinal surgery: National suspected cauda equina syndrome (CES) pathway

Cauda Equina Syndrome (CES) is a rare but serious spinal condition and if not diagnosed and treated swiftly, it can result in lifechanging injury. Nearly a quarter of compensation claims for spinal surgery in England relate to CES. This CES pathway and accompanying guidance by the Getting It Right First Time (GIRFT) programme, aims to provide healthcare professionals working in all care settings with the ability to effectively diagnose and care for patients presenting with suspected Cauda Equina Syndrome.

9 Sickle Cell Society: Standards for the clinical care of adults with sickle cell disease in the UK

These standards for the clinical care of adults with sickle cell disease were produced by the Sickle Cell Society in collaboration with a broad multi-disciplinary group of healthcare providers, patients and support groups.

10 HSIB: Management of sickle cell crisis

In this investigation, the Health Services Safety Investigation Body (HSSIB) used a real patient safety incident to explore how sickle cell crises are managed within hospital settings. In particular, the investigation considered:

• the knowledge nursing staff may have about the care of patients in sickle cell crisis
• how patient-controlled analgesia (PCA) – where a patient can use a device to give themself doses of pain relief medication – is considered holistically, such as monitoring the patient and staff workload.

11 Medication supply issues: Mast cell activation syndrome (MCAS)

Joy Mason is the Director of Operations, Services and Engagement at Mast Cell Action. In this blog, Joy tells us more about Mast Cell Activation Syndrome and how medication supply issues are impacting people’s lives and causing avoidable harm. 

12 Neonatal herpes – more common than you think?

Neonatal herpes is a rare, and potentially fatal, disease which usually occurs in the first four weeks of a baby's life. It is caused by the same virus that causes cold sores and genital infections – the herpes simplex virus (HSV). Early recognition and treatment has been shown to significantly improve babies' chances of making a full recovery. Sarah de Malplaquet, Chief Executive and Founder of the Kit Tarka Foundation, explains why they are joint-funding new research into neonatal herpes, and how the findings could help save many lives. 

13 What can I do to prevent my baby getting neonatal herpes? (Kit Tarka Foundation)

There are some simple things you can do to help prevent babies from catching herpes infections. These include regular hand washing, covering cold sores and not kissing babies who are not your own. The Kit Tarka Foundation provide information on neonatal herpes and how to keep your baby safe.

14 Creon shortages: “It’s just another thing patients with cystic fibrosis could do without”

There is a current shortage of Creon, a pancreatic enzyme replacement therapy. Sophie, a patient with cystic fibrosis, tells us about her experience of trying to get hold of Creon and the challenges she has faced.

15 From diagnosis to system change: what rare disease is teaching us about safety, bias and AI

Professor Rob Galloway is an Emergency Medicine Consultant and Founder of the charity Rare People. In this article, Rob talks about his daughter’s recent diagnosis of a rare genetic condition. He describes the barriers to safe and equitable care for people with rare diseases, and his hopes for future treatment development, supported by AI.

16 Equity for Rare: Delivering fair healthcare systems for people affected by rare conditions

The Genetic Alliance UK 'Equity for Rare' report highlights the inequities the rare conditions community experiences, and found that equity broadly means ensuring that people with rare conditions can navigate the healthcare system with the same dignity and efficacy as those with common conditions. It's gives five recommendations for the Government.

For more resources, take a look at our Rare diseases area of the hub.

Do you have a resource or story to share about rare diseases? Could your insights or experiences help improve patient safety? Leave a comment below (join the hub for free first) or contact us at content@pslhub.org.

• 86% of those who waited over five years for a diagnosis said it negatively impacted their ability to complete everyday tasks.
• 73% reported a negative effect on their mental health.
• 66% of working individuals said their condition impacted their ability to work effectively.
• Only 16% of respondents felt they had sufficient access to information and support.
• Just 26% had confidence in their GP’s understanding of their condition.

RAIRDA is calling for urgent action. The report sets out a series of practical policy recommendations, including:

• The introduction of clear and measurable targets for timely referrals and treatment.
• A named care coordinator for every person with a RAIRD.
• Increased investment in research to improve diagnostic pathways.

Interactive pathway

People living with rare diseases, such as muscular dystrophies or Huntington’s disease, can go through multiple appointments and referrals before a diagnosis is made due to the complexity of conditions, making it difficult for individuals and their families to coordinate their care.

The action plan, published today, includes 16 commitments to further improve care and has been developed in partnership with NHS England and NHS Improvement, the National Institute for Health and Care Excellence, Health Education England, Genomics England, the National Institute for Health Research, NHS Digital and the Medical Research Council.

Drawing on the UK’s strengths as a global leader in science, the Action Plan includes commitments on research, including an announcement of £40 million of new funding to the National Institute for Health Research (NIHR) BioResource, to further their work in characterising and understanding rare diseases.

Actions include:

• Improvements to newborn screening so diagnoses can be made earlier, including a new research pilot using whole genome sequencing to screen for rare genetic conditions in healthy newborns, and improvements to the way the UK National Screening Committee makes decisions on rare diseases
• A new digital tool called ‘GeNotes’, which will allow healthcare professionals to quickly access information on rare diseases to improve diagnosis so they can provide the right care for their patients
• Developing a toolkit for virtual consultations to increase the effectiveness of videoconference and telephone clinic calls, making it easier for patients to coordinate care between multiple specialists without the need to travel long distances
• Supporting access to new treatments through new programmes like the Innovative Medicines Fund, while continuing to work with NICE on new treatments being assessed.
• Monitoring uptake of drugs for patients with rare diseases to, by measuring the number of people accessing a drug and comparing with the number expected to access it, to ensure equal access to treatment across the country.

Pilot new approaches to care for patients with undiagnosed rare conditions. Following consultation with rare disease patients and their families, these pilots are currently under design, but examples could include a holistic one-stop paediatric clinic or a more targeted adult neurology clinic, or the use of virtual expert multidisciplinary teams.

You can also download it from the attachment.

• Recommendation one: Review and refresh the UK Strategy for Rare Diseases before the end of 2020. The strategy has become obsolete as technologies, policies and systems have moved on. Its commitments urgently need updating to ensure rare disease patients receive high quality services, treatment and support regardless of where they live in the UK.
• Recommendation two: Improve diagnosis and early intervention. Make the most of data and technologies for faster and more accurate diagnosis of rare diseases. Realise the value of the UK’s investment in genomics to ensure that rare and genetic conditions are identified as soon as possible, improving health outcomes and saving money for the NHS.
• Recommendation three: Modernise rare disease care and treatment. Introduce a comprehensive culture of best practice in the NHS, delivering evidence-based and coordinated care.
• Recommendation four: Enable people living with rare diseases to access accurate information. The NHS should provide information about rare conditions and signpost to support groups.
• Recommendation five: Protect and enhance the UK’s role in rare disease research. Ensure capacity for, and commitment to, research into rare diseases is not diminished and that the UK continues to attract investment.