Bones
Abnormally shaped head, pseudofractures, bone deformities, softening of bones, rickets*, frequent fractures, persistent musculoskeletal pain, waddling gait
What is HPP ?
Hypophosphatasia (HPP) is a rare, inherited and progressive metabolic disease characterised by defective mineralisation (the process that hardens and strengthens bones and teeth), impaired calcium and phosphate regulation and nonskeletal manifestations, such as muscle weakness, generalised fatigue and pain.1-3
HPP is caused by deficient activity of an enzyme known as alkaline phosphatase (ALP), which is important for building healthy bones as well as proper function of muscles.1
ALP deficiency can lead to poor growth and development and a variety of skeletal and nonskeletal abnormalities, including soft bones, deformity of bones, bone fractures, muscle weakness, fatigue, abnormal gait, early loss of primary teeth with the root intact and progressive damage to vital organs.1,2
As a result, the disease can have a debilitating impact, including loss of physical function and chronic pain.1
Signs and symptoms may vary and can impact many different parts of the body, including:
Symptoms can appear at any age and accumulate or worsen over time, causing significant disability, impaired mobility or life-threatening complications. References.1-3,7-10
Muscles and joints
Muscle weakness, neuromuscular pain, generalised body pain, joint stiffness or swelling, fatigue, arthritis, fibromyalgia
Ribs and lungs
Underdeveloped ribs and lungs†, severe breathing difficulties*, respiratory failure*
Central nervous system
Pain, headaches, vitamin B6-dependent seizures†, brain fog, depressed mood
Kidneys
Kidney stones, decreased kidney function
Teeth
Early loss of primary teeth with the root intact*, gum disease
*Signs and symptoms in infants and/or young children.
†Signs and symptoms in infants.
References
- Rockman-Greenberg C. Hypophosphatasia. Pediatric Endocrinology Reviews. 2013;10(2):380-388.
- Dahir KM, et al. Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry. Orphanet J Rare Dis.2022;17(1):277.
- 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):2171-2178.
- Uday S, et al. Tissue non-specific alkaline phosphatase activity and mineralization capacity of bi-allelic mutations from severe perinatal and asymptomatic hypophosphatasia phenotypes: results from an in vitro mutagenesis model. Bone. 2019;127:9-16.
- Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 2010;1192:190-200.
- Fang S, et al. Diagnosed prevalence of hypophosphatasia in the United States: a real-world analysis of electronic health records [poster]. Poster presented at: Annual International Conference on Pharmacoepidemiology and Therapeutic Risk Management; 23-27 August 2023, Halifax, Nova Scotia, Canada.
- Weber TJ, et al. Burden of disease in adult patients with hypophosphatasia: results from two patient-reported surveys. Metabolism. 2016;65(10):1522-1530.
- Whyte MP, et al. Natural history of perinatal and infantile hypophosphatasia: a retrospective study. J Pediatr. 2019;209(4):116-124.
- Beck C, et al. Whole-body MRI in the childhood form of hypophosphatasia. Rheumatol Int. 2011; 31(10):1315-1320.
- Khan AA, et al. Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults. Osteoporos Int. 2024; 35(3):431-438.
- Brandi ML, et al. The challenge of hypophosphatasia diagnosis in adults: results from the HPP international working group literature surveillance. Osteoporos Int. 2024;35(3):439-449.
Veeva ID: GL/UNB-H/0053