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

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.

Duke Scholars

Author Priya Sunil Kishnani Pediatrics, Medical Genetics