Bone Abstracts

Objectives: Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all age. Therefor diagnosis is often difficult and delayed. To improve the understanding of HPP in children and in order to shorten the diagnostic time span in the future we studied the natural history of the disease in our large cohort of pediatric patients. In light of the recently approved enzyme replacement therapy (asfotase alfa, a recombinant mineral-targeted TNAP) HPP patients may benefit from early treatment in the course of the disease.

Methods: This single centre retrospective chart review included longitudinal data from 50 patients with HPP diagnosed and followed at the University Children’s Hospital Wuerzburg, Germany over the last 25 years.

Results: The cohort comprises 4 (8%) perinatal, 17 (34%) infantile, 28 (56%) childhood and 1 (2%) Odonto-HPP. 2 patients were deceased at the time of the data collection. Diagnosis was based on available characteristic clinical symptoms (in 72%), available low AP activity (88%), accumulating substrates (in 56%) and X-ray findings (in 34%). Genetic analysis was performed in 47 patients (33 compound heterozygous) allowing investigations on genotype-phenotype correlations. Median age at first clinical symptoms was 3 months (min 0, max 107) and median time to diagnosis was 13 months (min 0, max 103) based on anamnestic data. Common symptoms included: delay of motor development (in 38 cases, 76%), bone pathologies (36, 72%), failure to thrive (31, 62%), premature loss of teeth (31, 62%) and musculoskeletal pain (24, 48%). Fourteen patients started medical treatment with asfotase alfa.

Conclusion: Findings reported support our clinical impression of a chronic multi-systemic disease with often delayed diagnosis. Our natural history information provides detailed insights into the prevalence of different symptoms which can help to improve and to shorten diagnostics and thereby lead to an optimised medical care.

Disclosure: The authors declared no competing interests.