What is HPP?

In HPP, persistently low ALP activity manifests as impaired bone mineralisation, muscle weakness and other systemic manifestations.1

It is crucial that age- and sex-adjusted normal reference ranges are used to assess persistently low ALP activity, especially in children who have higher normal ranges than adults.2–7
About HPP and low ALP

In children with HPP, premature loss of deciduous teeth, bone deformity and failure to thrive are characteristic manifestations of the disease.9

Adults with HPP typically present with pain, recurrent and poorly healing fractures that frequently require surgical intervention.10

Diagnosis of HPP can be confirmed by persistently low ALP and one or more characteristic clincal sign and symptom, including those seen on radiological
findings.2-7,11,12
Signs and symptoms

HPP often has a negative impact on the physical and mental wellbeing of children and adolescents, limiting their physical and emotional abilities in daily life and resulting in a lower quality of life.14

The pain, frequent fractures and surgical procedures experienced by adult patients with HPP results in significant limitations in their daily lives and severe emotional and psychological distress.12,15
Burden of disease
Fenn JS, et al. Hypophosphatasia. J Clin Pathol. 2021;74(10)635–640. ARUP. Alkaline phosphatase isozymes, Serum or plasma. Available at: https://ltd.aruplab.com/Tests/Pub/0021020. Last accessed February 2024. Colantonio DA, et al. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012;58:854–868. Adeli K. Biochemical Marker Reference Values across Pediatric, Adult, and Geriatric Ages: Establishment of Robust Pediatric and Adult Reference Intervals on the Basis of the Canadian Health Measures Survey. Clin Chem. 2015;61(8):1049–1062. Schumann G. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C. Part 9: Reference procedure for the measurement of catalytic concentration of alkaline phosphatase. Clin Chem Lab Med. 2011;49(9):1439–1446. Quest Diagnostics. Alkaline phosphatase. Available at: https://testdirectory.questdiagnostics.com/test/test-detail/234/alkaline-phosphatase?cc=MASTER. Last accessed February 2024. Labcorp. Alkaline phosphatase. Disponible à l’adresse suivante : https://www.labcorp.com/tests/001107/alkaline-phosphatase. Dernière consultation : février 2024. Linglart A, Biosse-Duplan M. Hypophosphatasia. Curr Osteoporos Rep. 2016;14:95–105. Högler W, et al. Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskeletal Discord. 2019;20(1):80. Seefried L, et al. Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry. J Bone Miner Res. 2010;35(11):2171–2178. Bishop N. Transformative therapy in hypophosphatasia. Arch Dis Child. 2016;101(6):514–515. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(Suppl 2):380–388. Szabo S, et al. Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review, Orphanet J Rare Dis. 2019;14(1):85; Rush ET, et al. Burden of disease in pediatric patients with hypophosphatasia: results from the HPP Impact Patient Survey and the HPP Outcomes Study Telephone interview. Orphanet J Rare Dis. 2019;14(1):201; Weber TJ, et al. Burden of disease in adult patients with hypophosphatasia: Results from two patient-reported surveys. Metabolism. 2016;65(10):1522–1530.