CASE REPORT article
Front. Endocrinol.
Sec. Pediatric Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1587807
Case report: a suboptimal response to the standard dose of asfotase alfa in a patient with perinatal hypophosphatasia. Can we do better?
Provisionally accepted- 1University Hospital Centre Zagreb, Zagreb, Croatia
- 2Department of Paediatrics, School of Medicine, University of Zagreb, Zagreb, Zagreb, Croatia
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Hypophosphatasia (HPP) is a rare, inherited metabolic disorder due to deficiency of tissue-nonspecific alkaline phosphatase, characterized by defective bone and teeth mineralization with consequent problems, including respiratory failure characteristic for severe types of HPP. Severe patients exhibit other disease-related manifestations, including neurological, which make HPP complex and difficult to manage. Enzyme replacement therapy with asfotase alfa is the disease-specific treatment for skeletal manifestations in pediatric patients. We present a patient with perinatal HPP who had a severe clinical course with respiratory insufficiency during infancy requiring a higher dose of asfotase alfa than recommended (12 mg/kg/week). After improvement of respiratory function and outgrowing the higher dose, the patient was maintained on the standard dose (6 mg/kg/week) from the age of three years. At six years of age, unexplained clinical and radiographic deterioration occurred while laboratory parameters remained normal. Following traumatic humerus fracture that occurred after several months, asfotase alfa was increased to 10 mg/kg/week. Remarkable clinical improvement was observed and the patient regained the ability to walk unassisted three months after the dose correction. Rickets severity score changed from 10 to 3.5 within 14 months. No side effects of higher drug dose have been noticed. The remaining challenge in this patient is neurodevelopmental disorder. Conclusion: The standard dose of asfotase alfa was not sufficient to treat skeletal manifestations of HPP in our patient, indicating that some perinatal HPP patients should be treated with higher doses to reach treatment goals. Although bone disease and patient outcomes have been improved with tailored drug doses, neurological manifestations of HPP remain challenging.
Keywords: Alkaline Phosphatase, Hypophosphatasia, Perinatal form, Asfotase alfa, Rickets, Central Nervous System
Received: 05 Mar 2025; Accepted: 20 May 2025.
Copyright: © 2025 Petković Ramadža, Žigman, Čavka and Barić. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ivo Barić, University Hospital Centre Zagreb, Zagreb, Croatia
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