Life sciences Policy, research + analysis

Out of the shadow: Transforming care for people living with hypophosphatasia

June 2025

Out of the shadow: Transforming care for people living with hypophosphatasia

Hypophosphatasia (HPP) is a genetic, multisystem condition that impairs the body’s ability to properly mineralise bones and teeth, leading to weakened bones, fractures, deformities, and early tooth loss. It is one of more than 7000 life threatening or chronically debilitating rare diseases, that around 2 million Australians live with each day.

Rare diseases in Australia

A disease is considered rare if it affects fewer than 1 in 2,000 people.

More than 7,000 rare diseases that are lifethreatening or chronically debilitating.

Around 8 per cent of Australians (2 million people) live with a rare disease.

HPP can affect individuals at any stage, from neonates to adults, with a broad spectrum of severity, ranging from life-threatening manifestations to more subtle signs that are often overlooked.

HPP can result in stillbirth or infant mortality.

Median survival for untreated infants with HPP is 8.9 months with 42 per cent 1 year survival and 27 per cent 5 year survival.

Even non-life-threatening forms of HPP can cause significant discomfort and disability. People living with HPP have nearly double the level of disability compared to the general population. Ultimately, this affects how they participate in society, as well as their economic security. They desperately need a health system that recognises and supports them to decrease this burden.

A global registry study on HPP revealed that:

Among paediatric patients,
36 per cent use wheelchairs, 32 per cent require crutches, and 27 per cent use canes.

For adults, 27 per cent use crutches, while 21 per cent require walkers and/ or canes.

86 per cent of adults have experienced at least one fracture, with an average of nearly 13 fractures per person.

Given its broad and variable symptoms, HPP is often misdiagnosed or overlooked, resulting in delayed diagnoses, limited treatment options, and fragmented care.

Australians with HPP can wait up to 24 years for a diagnosis, with key indicators like persistently low alkaline phosphatase levels frequently missed.
Despite being a complex, lifelong condition, there is no national model of care for HPP, leaving most patients to coordinate their own multidisciplinary care across a disjointed system.
Australia’s current system for approving and funding new therapies is not fit for rare diseases, creating barriers through lengthy assessments and unrealistic evidence requirements—making access to promising treatments unnecessarily difficult.

HPP is a clear example of where the system breaks down. But it’s also a unique opportunity to show how it can be rebuilt. Targeted, achievable reforms to improve diagnosis, treatment access and care coordination for people with HPP would not only transform lives for this small, high-need group — they would road-test solutions for the broader rare disease community.

The challenges faced by Australians with HPP are not isolated — they are symptoms of a broader failure in how the health system responds to rare diseases.

Our report Out of the shadow proposes four recommendations that outline practical, scalable reforms that respond directly to system gaps exposed by HPP — and create a model for change across the rare disease landscape.

Standardise pathology reporting to include alerts when ALP falls below normal range, to enable early recognition and referral of suspected HPP.

Develop Australian specific clinical guidelines and patient education materials for HPP and make them publicly available on the Rare Awareness Rare Education (RARE) Portal.

Progress HTA Review recommendations relevant to accessing therapies for rare and ultra-rare diseases, like HPP.

Fund the development of a national model for rare disease centres of expertise, including access to bone disease specialist care, care coordination and virtual service delivery for HPP patients.

References

Genetic and Rare Diseases Information Centre. Hypophosphatasia 2025; Available from: https://rarediseases.info.nih.gov/diseases/6734/hypophosphatasia.
Fenn, J.S., et al., Hypophosphatasia. Journal of Clinical Pathology, 2021. 74(10): p. 635.
Khan, A.A., et al., Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults. Osteoporos Int, 2024. 35(3): p. 431-438.
Australian Government – Department of Health and Aged Care. What we’re doing about rare diseases. 2022; Available from: https://www.health.gov.au/topics/chronic-conditions/what-were-doing-about-chronic-conditions/what-were-doing-about-rare-diseases.
Rockman-Greenberg, C., Hypophosphatasia. Pediatr Endocrinol Rev, 2013. 10 Suppl 2: p. 380-8.
Szabo, S.M., et al., Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review. Orphanet Journal of Rare Diseases, 2019. 14(1): p. 85.
Whyte, M.P., et al., Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. The Journal of Clinical Endocrinology & Metabolism, 2016. 101(1): p. 334-342.
Seefried, L., et al., Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry. J Bone Miner Res, 2020. 35(11): p. 2171-2178.
Weber, T.J., et al., Burden of disease in adult patients with hypophosphatasia: Results from two patient-reported surveys. Metabolism, 2016. 65(10): p. 1522-30.
Högler, W., et al., Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC
Musculoskelet Disord, 2019. 20(1): p. 80.
Medicines Australia. HTA and rare diseases. 2022; Available from: https://www.medicinesaustralia.com.au/wp-content/uploads/sites/65/2022/11/HTA-DP-Rare-Disease.pdf.