Clinical Profiles of Children with Hypophosphatasia prior to Treatment with Enzyme Replacement Therapy: An Observational Analysis from the Global HPP Registry

Gabriel Ángel Martos-Moreno; Cheryl Rockman-Greenberg; Keiichi Ozono; Anna Petryk; Priya S Kishnani; Kathryn M Dahir; Lothar Seefried; Shona Fang; Wolfgang Högler; Agnès Linglart

doi:10.1159/000531865

Clinical Profiles of Children with Hypophosphatasia prior to Treatment with Enzyme Replacement Therapy: An Observational Analysis from the Global HPP Registry

Horm Res Paediatr. 2024;97(3):233-242. doi: 10.1159/000531865. Epub 2023 Jul 13.

Authors

Affiliations

¹ Departments of Pediatrics and Pediatric Endocrinology Hospital Infantil Universitario Niño Jesús, IIS La Princesa, Universidad Autónoma de Madrid, CIBERobn, ISCIII, Madrid, Spain.
² Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
³ Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁴ Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA.
⁵ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
⁶ Division of Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Orthopedic Department, University of Würzburg, Würzburg, Germany.
⁸ Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria.
⁹ Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
¹⁰ AP-HP, Paris-Saclay University, service d'endocrinologie et diabète de l'enfant, DMU 3 SEA, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Filière OSCAR; Paris-Saclay University, INSERM U1185, Bicêtre Paris-Saclay Hospital, Le Kremlin-Bicêtre, Paris, France.

Abstract

Introduction: The objective of this study was to better understand the clinical profiles of children with hypophosphatasia (HPP) prior to treatment with enzyme replacement therapy (ERT).

Methods: Pretreatment demographics and medical histories of ERT-treated children (aged <18 years) enrolled in the Global HPP Registry (2015-2020) were analyzed overall, by age at first HPP manifestation (<6 months vs. 6 months to 18 years), and by geographic region (USA/Canada, Europe, and Japan).

Results: Data from 151 children with HPP were analyzed. Sex distribution was balanced overall (52.3% female; 47.7% male) but differed in Japan (63.0% female; 37.0% male). Prior to ERT initiation, common manifestations were skeletal (67.5%) and extraskeletal, with the foremost types being muscular (48.3%), constitutional/metabolic (47.0%), and neurologic (39.7%). A high proportion of children who first presented at <6 months of age (perinatal/infantile period) had a history of bone deformity (59.3%) and respiratory failure (38.3%), while those aged 6 months to 18 years at first manifestation had a predominance of early loss of primary teeth (62.3%) and gross motor delay (41.0%). Those from Japan were reported to have a younger median age overall, the highest proportion of skeletal manifestations (80.4%) and growth impairment, while European data reported the highest proportion of muscular manifestations (70.7%). In the USA/Canada, skeletal and muscular manifestations were reported at the same frequency (57.4%).

Conclusion: Prior to ERT, skeletal and extraskeletal manifestations were commonly reported in children with HPP, with differences by age at first HPP manifestation and geographical region. Comprehensive assessments of children with HPP are warranted prior to ERT initiation.

Keywords: Alkaline phosphatase; Disease burden; Enzyme replacement therapy; Hypophophatasia.

Publication types

Observational Study
Multicenter Study

MeSH terms

Adolescent
Canada / epidemiology
Child
Child, Preschool
Enzyme Replacement Therapy*
Female
Humans
Hypophosphatasia* / drug therapy
Hypophosphatasia* / epidemiology
Infant
Infant, Newborn
Male
Registries*

Grants and funding

This study was sponsored by Alexion, AstraZeneca Rare Disease, Boston, MA, USA. The Global HPP Registry is sponsored by Alexion, AstraZeneca Rare Disease and is overseen by a scientific advisory board comprised clinical experts in hypophosphatasia, including employees of Alexion, AstraZeneca Rare Disease, who held roles in the conception and design of the Global HPP Registry and this study, the collection of data, the statistical analyses, the interpretation of data, and writing of the manuscript as described in the Author Contributions section.