Bone Abstracts

Objectives: Limited data exist on growth parameters in children with hypophosphatasia (HPP), a rare metabolic disease characterized by impaired bone mineralization. We aimed to describe growth characteristics in untreated children with HPP enrolled in the Global HPP Patient Registry.

Methods: Children (<18 years old) with a diagnosis of HPP who were not receiving enzyme replacement therapy with asfotase alfa at the time of evaluation were identified from the registry, and data on their clinical characteristics and first and last available growth assessments, including height and weight (prior to treatment if previously treated), were extracted. Median (min, max) z-scores were calculated using World Health Organization and Centers for Disease Control and Prevention standards.

Results: Of the 194 children (59% female) included, median (min, max) age at first HPP manifestation was 1.1 (–0.5, 16.9) years (n=161). The most common first clinical HPP manifestations were premature loss of deciduous teeth (52% of patients), bone deformities (32%) and failure to thrive (21%); 53% of patients had experienced ≥3 clinical HPP manifestations and 48% had manifestations in ≥3 organ systems. Of the patients born full term (92% of patients with data), height z-score at first assessment was –0.2 (–6.3, 3.2), with 18% of patients below the third percentile, and weight z-score was 0.0 (–4.1, 7.1), with 8% below the third percentile. For patients aged <2 years at assessment, change in length z-score was –1.2 (–5.1, 2.5) over a median (min, max) of 1.1 (0.0, 2.0) years, whereas height z-score remained relatively consistent in patients aged ≥2 years (z-score change 0.0; –6.1, 5.0) over a median of 1.5 (0.0, 16.0) years. For patients born small for gestational age (SGA; n=13), height and weight z-scores increased over time, but decreased for patients who were not SGA (n=109). Height z-score did not correlate significantly with the number of HPP manifestations experienced.

Conclusion: These data suggest growth worsens over time in patients aged <2 years but remains relatively unchanged for those ≥2 years. Furthermore, height may not be predictive of disease severity in children.

Disclosure: Wolfgang Högler, Agnès Linglart, Priya Kishnani, Lothar Seefried, Cheryl Rockman-Greenberg, Keiichi Ozono and Gabriel Ángel Martos-Moreno are consultants for, and have received research funding and honoraria from, Alexion Pharmaceuticals, Inc. Anna Petryk and Shona Fang are employees of, and may own stock/options in, Alexion Pharmaceuticals, Inc., which sponsored the study.