The diagnosis of a rare disease cannot rely on chance
What hypophosphatasia can teach us about finding patients sooner
This work has been funded by Alexion, AstraZeneca Rare Disease
For too many people living with a rare condition, diagnosis remains a long and uncertain journey. In the UK, more than a third of people with a rare condition wait over five years from first experiencing symptoms to receiving a final diagnosis.1
This is the well-recognised ‘diagnostic odyssey’ in rare disease. Advances in genomics, diagnostics, and data are helping some conditions to be identified earlier, but technology alone cannot close the gap.2 People can still fall between the cracks when symptoms are considered in isolation, routine clinical clues are overlooked, or there is no clear route from suspicion to specialist assessment.
Rare bone conditions illustrate this challenge clearly. Fractures, bone or joint pain, muscle weakness, fatigue, and mobility problems can all point to an underlying rare bone condition – but they can also resemble much more common conditions such as osteoporosis or even non-bone related conditions like fibromyalgia.3,4
This is particularly true for hypophosphatasia (HPP), a rare inherited metabolic bone condition that can affect people at any age.1 People with HPP often experience repeated fractures, bone and joint pain, muscle weakness, long-term fatigue, and significant mobility problems.5 In children, growth and development can also be affected, while severe infantile HPP can even be fatal.3 As a result, HPP can have a significant impact not only on those living with the condition, but also on their families and carers.
Early recognition and specialist assessment are therefore essential. HPP continues to be misdiagnosed and important biochemical clues available through routine testing are frequently overlooked.6 Once again, an ongoing challenge in rare diseases.
To help change this reality, Alexion, with the support of Metabolic Support, those with lived experience of the condition, and leading clinicians from across the rare bone disease community, has developed the Think Rare, Think HPP Blueprint.
The Blueprint sets out what an optimal HPP diagnostic pathway should look like, alongside practical clinical, system and policy recommendations to help make it a reality. Importantly, the methodology used to develop the Blueprint has been designed with broader application in mind, providing an approach that could be adapted to other rare conditions facing similar challenges in diagnosis and referral.
“Too many people living with HPP face long delays before receiving an accurate diagnosis; we need change. The Think Rare, Think HPP Blueprint is an authentically impactful pathway - meaningfully aggregating the voices and experiences of the people involved in improving diagnosis - designed to improve clinical expertise, patient experience and practical recommendations to support earlier recognition, more consistent referrals and better outcomes for people affected by HPP.”
Kirsty Hoyle, Chief Executive of Metabolic Support
The Think Rare, Think HPP Blueprint will be launched at a parliamentary drop-in event on 28 October, ahead of World HPP Day on 30 October. The event will bring together those involved in shaping the Blueprint, alongside parliamentarians to build support for earlier and more consistent diagnosis in rare conditions.
The event comes at an important time as the Government considers the future of rare disease policy in the UK, with the next iteration of the UK Rare Disease Framework expected to be published in February next year. HPP provides a timely reminder of why faster diagnosis must remain central to what comes next, and why future policy must not overlook rare conditions where important clinical clues may already be available through routine NHS care.
“HPP shows that there are practical opportunities to recognise the signs of rare disease earlier and improve the route into specialist care. As the Government considers the future of rare disease policy, we need to make sure faster diagnosis remains a priority.”
Bob Blackman MP
If we are serious about shortening the diagnostic odyssey in rare disease, we need to make sure that the clues already available to us lead to action.
M/UK/UNB-H/0146 | Date of preparation: September 2026
References
- Association of British Pharmaceutical Industry (n.d.). Rare disease, The diagnosis challenge. Available at: https://www.abpi.org.uk/rare-diseases/thediagnosis-challenge/ (Accessed September 2026).
- Genetic Alliance UK (n.d.). Improving genomic research and services. Available at: https://geneticalliance.org.uk/campaigns-and-research/improving-genomicresearch-and-services/ (Accessed September 2026).
- Soft Bones UK (2018). What is HPP? Available at: https://www.softbonesuk.co.uk/what-is-hpp/ (Accessed September 2026).
- Rodríguez-Araya, L et al. (2025). The Challenge of Hypophosphatasia Diagnosis in Patients with Fibromyalgia. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC13046356/ (Accessed September 2026).
- Conti, F et al. (2017). Hypophosphatasia: clinical manifestation and burden of disease in adult patients. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC5726215/ (Accessed September 2026).
- Vidal, M et al. (2026). Hypophosphatasia: current concepts in diagnosis and management of a rare metabolic disorder. Available at: https://www.explorationpub.com/Journals/emd/Article/1007135 (Accessed September 2026).
