ESPE Abstracts

Background: Hypophosphatasia (HPP) is the rare inherited metabolic disease resulting from loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Understanding of the clinical presentation is largely based on single case reports, which presents challenges for the recognition and diagnosis of HPP.

Objective: To better understand disease presentation, we surveyed the literature to characterize clinical features and presentation for children under the age of 18 with HPP.

Methods: English-language cases were identified through searches of PubMed using the keywords ‘hypophosphatasia’ AND (‘case report’ OR ‘case study’) and reference lists of identified articles. Cases were then filtered for those reporting patients under age 18. Available information captured for each case included: age of patient, presenting features, predetermined systemic manifestations of interest including craniosynostosis, respiratory compromise, and nephrocalcinosis, and age at death if applicable.

Results: 293 publications were identified, dating from 1939; of which, 166 publications reported 365 cases <18 years of age. 141 cases had perinatal onset, 68 infantile onset (<6 months of age), and 78 juvenile onset (6 months, <18 years) of HPP; 23 had dental manifestations only (odontohypophosphatasia) and 55 did not provide enough information to determine age at onset. 142 patients were reported as deceased (range of age at death: prenatal to 16 years). Common first reported symptoms included skeletal deformities, failure to thrive, respiratory difficulties, seizures, or premature tooth loss. Overall, the most frequently reported manifestations of interest were premature tooth loss (n=114), respiratory complications (n=108), craniosynostosis (n=77), and muscle weakness (n=73). Other commonly reported complications included delayed walking/motor development and failure to thrive. 40 patients had undergone surgery for craniosynostosis and 12 for correction of deformity or fracture fixation.

Conclusion: Recognition of these common symptoms as characteristic of hypophosphatasia will facilitate proper diagnosis of this rare disease.

Declaration of interest: E K Sawyer and K Anderson are employees of Alexion Pharmaceuticals, Inc.