Hypophosphatasia (HPP) is a rare, inherited, systemic disease caused by mutation(s) of the ALPL gene encoding tissue-nonspecific alkaline phosphatase (ALP), resulting in deficient ALP activity. Asfotase alfa is an enzyme replacement therapy approved for treatment of patients with pediatric-onset HPP. The global HPP Registry is an observational, prospective, multinational study (NCT02306720; EUPAS13514) established to collect real world clinical data from patients of all ages with HPP, regardless of asfotase alfa treatment status. We report characteristics of children aged <18 y enrolled in the HPP Registry by asfotase alfa treatment status at enrollment. Children included in this analysis had signs and symptoms consistent with a diagnosis of HPP confirmed by low serum ALP activity and/or ALPL mutation; deceased patients were not included per protocol. Of 269 patients enrolled from 11 countries from January 2015 through September 2017, 121 (45.0%) were children, of whom 45 (37.2%) were being treated with asfotase alfa at enrollment and 76 (62.8%) were untreated. Of the treated patients, 16 were former participants in asfotase alfa clinical studies. Treated children were mostly female (66.7%) and Asian (67.4%); untreated children were mostly female (57.9%) and white (73.5%). Median (min, max) age at earliest HPP manifestation was 0 (−0.2 y, 4.3 y) for treated children and 2.2 years (0, 15.9 y) for untreated children. Median (min, max) age at time of diagnosis was 0 (−0.02 y, 13.2 y) for treated children (diagnostic delay: 1.1 d [0, 11.5 y]) and 3.3 years (0, 16.0 y) for untreated children (diagnostic delay: 0.7 y [0, 10.7 y]). Medical histories showed that patients frequently reported skeletal signs and symptoms (treated: 75.6%; untreated: 25.3% [e.g., bone deformity, rickets, fractures]), failure to thrive (treated: 46.7%; untreated: 14.7%), respiratory support (treated: 46.5%; untreated: 2.7%), neurologic manifestations (treated: 42.2%; untreated: 17.3% [e.g., developmental delay, craniosynostosis, seizures]), renal signs and symptoms (treated: 31.8%; untreated: 18.7% [e.g., hypercalcemia, nephrocalcinosis, hyperphosphatemia]), premature loss of deciduous teeth (treated: 25.0%; untreated: 59.5%), and muscular manifestations (treated: 15.9%; untreated: 21.3% [e.g., abnormal gait, weakness]). These data show that treated children with HPP presented at an earlier age and had minimal diagnostic delay compared with untreated children. Medical histories suggest that systemic manifestations of HPP are common among children with HPP. The Registry does not capture data from neonates and young infants, either treated or untreated, who died before enrollment, thus potentially underestimating or not reflecting the spectrum of disease burden in HPP.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology