Making the connection

Hypophosphatasia (HPP) in children and adolescents

Persistently low age- and sex-adjusted alkaline phosphatase (ALP) levels can be the key to identifying HPP in some hard-to-diagnose patients.^1,2

HPP can lead to a wide variety of multisystemic consequences³

Neurological symptoms were seen in ~27% of pediatric patients with HPP

Multinational observational, prospective Global HPP Registry study conducted in children (N=121; ≥18 years) from January 2015 - September 2017.

Chart detailing the multisystemic consequences of HPP

*Excludes patients aged <2 years at enrollment.

^†Excludes patients aged <6 months at enrollment.

In HPP, low alkaline phosphatase activity leads to an accumulation of pyridoxal 5’-phosphate (PLP) in the systemic circulation resulting in a deficiency of vitamin B₆ in the central nervous system, which can cause seizures (which is most common in infants)¹

Patient image is hypothetical.

Any clinical sign/symptom PLUS persistently low ALP is sufficient for an HPP diagnosis^1,4*

In children, what is considered “low ALP” is variable because ALP reference values are highly dependent on age and sex. Ensure that lab results for ALP levels reflect age- and sex-adjusted reference ranges for the specific patient. ^1,4-6

Learn how to determine if your patient’s ALP level is low.

Reduced ALP levels during childhood may affect peak bone mass^7,8

In adulthood, mineralization deficits can lead to risk for osteopenia and osteoporosis and to increased risk of fracture.⁹

Decreased bone mass in childhood may lead to a higher rate of fractures in adulthood.⁷

Percentage of patients with HPP fractures ^10-12

$Chart detailing the percentage of HPP patients with fractures$

*Data from a multinational noninterventional, retrospective chart review study designed to understand the natural history of 48 patients ≤5 years of age with severe perinatal- and infantile-onset HPP. Patients included in the study were those diagnosed with HPP based on at least one of the following: serum biomarker levels (below-normal ALP and above-normal PLP or PEA), below-normal ALP and radiographic abnormalities, and/or genetic analysis of the ALPL gene. Additionally, onset of HPP must have occurred prior to 6 months of age based on signs that included at least one of the following: respiratory compromise, rachitic chest deformity, and/or vitamin B₆–responsive seizures.²

^†Data from a retrospective, multinational, noninterventional natural history study of childhood HPP in patients 5 to 15 years of age (N=32). ³

^‡Combined data from HIPS/HOST, an Internet questionnaire and telephone survey that queried demographics, HPP-related illness history, disease progression, and health-related quality of life. One hundred twenty-five adults participated.⁴

Case Studies

Meet Hannah, 7

Her mother is concerned about her daughter’s short stature and fatigue

Meet Ronny, 11

Presenting with weakness and developmental delays

QUICK QUESTION

True or False?

What is considered “low ALP” in children varies across ages and sexes.

Answer:True. Be sure to check your patient’s ALP level against the lab’s age- and sex-adjusted reference interval, especially in children.

References: 1. Rockman-Greenberg C. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388. 2. Bianchi ML, et al. Osteoporos Int. 2020;31(8):1445-1460. doi: 10.1007/s00198-020-05345-9 3. Hӧgler W, et al. BMC Musculoskelet Disord. 2019;20(1):80. doi: 10.1186/s12891-019-2420-8 4. Colantonio DA, et al. Clin Chem. 2012;58(5):854-868. doi: 10.1373/clinchem.2011.177741 5. McKiernan FE, et al. J Bone and Miner Res. 2014;29(7):1651-1660. doi: 10.1002/jbmr.2178 6. Bishop N, et al. Arch Dis Child. 2016;101(6):514-515. doi: 10.1136/archdischild-2015-309579 7. Davies JH, et al. Arch Dis Child. 2005;90(4):373-378. doi: 10.1136/adc.2004.053553 8. Clarke J, et al. Accessed August 31, 2021. http://www.statcan.gc.ca/pub/82-624-x/2016001/article/14637-eng.pdf 9. Maggioli C, et al. Ann Pediatr Endocrinol Metab. 2017;22(1):1-5. doi:10.6065/apem.2017.22.1.1 10. Whyte MP, et al. J Pediatr. 2019;209:116-124:e4. doi: 10.1016/j.jpeds.2019.01.049 11. Whyte MP, et al. A retrospective, multi-national, non-interventional, natural history study of the childhood form of hypophosphatasia. Presented at: the Endocrine Society’s 97th Annual Meeting and Expo; March 15, 2015; San Diego, CA. 12. Weber TJ, et al. Metabolism. 2016;65(10):1522-1530. doi: 10.1016/j.metabol.2016.07.006