Signs and symptoms
HPP is often associated with a high clinical burden regardless of age at first manifestation.4 While HPP is frequently diagnosed during childhood, it may not be diagnosed until adulthood in some patients, even though patients may have had symptoms for years.1,2

The signs and symptoms may change and accumulate over a patient’s lifetime with the disease manifesting differently in adults and children.4,5

The typical manifestations of HPP in infants may include failure to thrive, rickets-like chest deformity, respiratory insufficiency, craniosynostosis, and vitamin B6-responsive seizures.1,5

In adults, common clinical features include muscle weakness, pain, dental abnormalities, abnormal gait, recurrent fractures and pseudofractures.1–3,5

List of HPP manifestations is not exhaustive.

List of HPP manifestations is not exhaustive.

*Adult patient may have had a history of symptom despite it not being currently present.
Real-world data from the Global HPP Registry: Proportion of children (n=151, %) with history of HPP-related clinical signs and symptoms17‡

Adapted from Martos-Moreno, et al. Horm Res Paediatr. 2024;97(3):233–242.17

*Excludes patients <6 months of age at enrolment.1

† The symptoms listed are not exhaustive, and there are other manifestations that may be present in children with HPP as detailed in the graph.
1,17

‡ The Global HPP Registry, sponsored by Alexion Pharmaceuticals, is an observational, longitudinal, multinational study with medical history data collected based on patient or parent/guardian recall; Patients may have more than 1 sign and symptom within each body system.17

§ There are multiple signs and symptoms that contribute to each category heading. Skeletal also includes: recurrent and poorly healing fractures/pseudofractures, osteomalacia (by biopsy) and chronic inflammation/bone marrow oedema; muscular include weakness, gross motor delay and abnormal gait (excludes patients < 2 years of age at enrolment); constitutional/metabolic includes failure to thrive and fatigue; neurologic include: craniosynotosis, cognitive delay/developmental delay, seizures and acute intracranial pressure; dental include early loss of primary teeth and other, which includes: loss of permanent teeth, loose teeth, poor dentition, hypodontia, dental implants, dental bridges, and dentures; renal includes hypercalcemia, hypercalciuria and hyperphosphatemia; respiratory includes: respiratory failure and pneumonia; pain includes: chronic bone pain, generalised body pain, chronic muscle pain and fibromyalgia; rheumatic includes: pseudogout and ectopic calcification.17
Real-world data from the Global HPP Registry - history of HPP-related clinical signs and symptoms, adults (n = 304), n/N (%):3‡

Adapted from Seefried L, et al. J Bone Miner Res. 2020;35(11):217 1–2178.3

*Dental problems include early loss of deciduous teeth, loss of permanent teeth and poor dentition.

†List is not exhaustive and there are other manifestations that may be present in adults with HPP.3

‡The Global HPP Registry, sponsored by Alexion Pharmaceuticals, is an observational, longitudinal, multinational study with medical history data collected based on patient or parent/guardian recall. This analysis was performed on data from 304 adults with a confirmed diagnosis of HPP.3
In infants, severe hypomineralisation may lead to near-total absence of bone, whereas children often show signs of rickets, osteopenia, and open growth plates. In adults, skeletal complications such as stress fractures, pseudofractures, and delayed fracture healing are common, affecting mobility and function19–22
*Lists are not exhaustive.
Adapted from Nunes ME. Hypophosphatasia. In: Adam MP, et al., eds. GeneReviews®. Seattle, WA: University of Washington; 1993–202219, Whyte MP, et al. J Bone Miner Res. 2018;33(5):868–87420, Hoffman C, et al. Clin Rev Bone Miner Metab. 2013;11(2):60–7021, and Whyte MP. Principles of Bone Biology. San Diego, CA: Academic Press; 2008:1573–1598.
*Lists are not exhaustive.
HPP, hypophosphatasia.
advance I am a healthcare professional registered in the EU I am not a
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