Volume 30, Issue 173, July 2026

Enzyme replacement therapy with asfotase alfa in children with hypophosphatasia – safety and effectiveness: narrative review

Ksenia Jakubiak^1♦, Julia Witkowska¹, Adam Brożyna², Agnieszka Mackiewicz³, Katarzyna Bielak⁴, Krystian Woźniak¹, Mikołaj Kurczyński¹, Monika Krasoń¹, Natalia Kursa¹, Aleksandra Pietrucień³

¹Central Teaching Hospital of the Medical University of Lodz: Łódź, 92-213, ul. Pomorska 251 PL
²University Clinical Hospital No. 1 of the Medical University of Lodz: Łódź, 90-153, ul. Kopcińskiego 22, PL
³Medical Center of Pabianice, Pabianice, 95-200, ul. Jana Pawła II 68, PL
⁴5 Military Clinical Hospital in Cracow, 30-901 Cracow, ul. Wrocławska 1-3, PL

^♦Corresponding author
Ksenia Jakubiak, Central Teaching Hospital of the Medical University of Lodz: Łódź, 92-213, ul. Pomorska 251 PL

ABSTRACT

Hypophosphatasia is a metabolic illness caused by mutations in the ALPL gene, which lead to impaired bone mineralization and multiple whole-body complications, including premature tooth loss. The implementation of enzyme replacement treatment (ERT) with asfotase alfa has provided a substantial role in the management and prognosis of children with hypophosphatasia. This review shows current data on the efficiency, safety, and limitations of ERT with asfotase alfa in pediatric patients. The literature search was conducted on PubMed. Articles were published between 2015 and 2025. Special attention was given to clinical studies, case reports, and review articles that included pediatric patients with hypophosphatasia who were enrolled in enzyme replacement therapy with asfotase alfa. The available evidence shows that asfotase alfa improves survival, bone mineralization, and quality of life. The ERT, moreover, ameliorates respiratory symptoms and mobility problems, especially in perinatal and infantile forms of hypophosphatasia. Early treatment yields better clinical outcomes. The therapy is generally well tolerated, and adverse effects are mostly mild. At the same time, there are some important unresolved issues, including limited long-term safety data and differences in therapy response. The treatment carries potential for immunogenicity. Unfortunately, scientists cannot specify the exact dosage of medicine and how long patients should be treated with it. Asfotase alfa is an effective and moderately safe treatment option for children with HPP. More research is needed to assess the long-term safety profile of outcomes. This is very important to find proper doses.

Keywords: hypophosphatasia, childhood hypophosphatasia, infantile hypophosphatasia, perinatal hypophosphatasia, odontohypophosphatasia, enzyme replacement therapy with asfotase alfa

Medical Science, 2026, 30, e132ms3929

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Published: 25 July 2026