ESPE Yearbook of Paediatric Endocrinology

In Brief: Hypophosphatasia is a clinically heterogenous disorder. By analysing observational data on 215 children (54.4% girls) with hypophosphatasia from the Global Hypophosphatasia Registry, the authors found growth impairment in patients aged <2 years. However, short stature was not a characteristic feature of children with hypophosphatasia, and height was not correlated with disease severity.

Commentary: Hypophosphatasia is an inborn error of metabolism characterized by impaired bone mineralization that often affects linear growth. A natural history study of longitudinal data collected from 101 patients over the course of 25 years at a single center in the United States showed that children with HPP may have below-average height but normal weight compared to the general population. Given that hypomineralization disorders can negatively affect the zone of hypertrophic chondrocytes of the growth plate, growth in children with HPP has often been suggested as an indicator of disease burden and overall health.

This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children (aged <18 years) with hypophosphatasia. Anthropometry was evaluated by age group (<2 years and ≥2 years). The frequency of hypophosphatasia manifestations was compared between children with and without short stature.

Short stature was present in 16.1% of children with hypophosphatasia aged <2 years, and in 20.4% of those aged ≥2 years. Among those with available data (n=62), height was below target height (mean −0.66 standard deviations). Substantial worsening of growth (mean delta height z score: −1.45; delta weight z score: −0.68) occurred before 2 years of age, but after age ≥2 years growth trajectories were maintained (delta height z score: 0.08; delta weight z score: 0.13). Broad-ranging hypophosphatasia manifestations (beyond dental) were observed in most children, with bone deformities, bone pain, failure to thrive, fatigue, and muscle weakness being the most common.

Short stature is not a consistent characteristic of children with hypophosphatasia, but growth impairment was observed in those aged <2 years, indicating that alkaline phosphatase activity is critical for growth plate function during the rapid growth of infancy. In addition, a broad range of clinical manifestations occurred in those above and below the 3rd percentile for height, indicating that height alone does not indicate hypophosphatasia severity and that weight is less affected than longitudinal growth.