With the advent of asfotase alfa, the enzyme replacement therapy (ERT) approved for hypophosphatasia (HPP), health care providers need to navigate management of ERT during critical illness.
We present the case of a young girl, treated with ERT for severe perinatal HPP, who had cardiorespiratory arrest in the setting of influenza A. Her life-saving treatment involving extra corporeal membrane oxygenation (ECMO) required a two-week interruption of ERT leading to persistent hypercalcemia and hyperphosphatemia. A three year old female presented with respiratory distress and blood tinged secretions. She was influenza A positive with bilateral opacities on chest X-ray (CXR). Worsening respiratory distress and bradycardic arrest required intubation, CPR and venoarterial ECMO cannulation. She remained on ECMO for 10 days with anticoagulation restrictions requiring her thrice-weekly subcutaneous ERT to be held. Hypercalcemia (12.3 mg/dL) and hyperphosphatemia (7.6 mg/dL) developed two weeks after restarting ERT and resolved six weeks later.
We highlight that the obligatory cessation of ERT while on ECMO led to the loss of functional TNSALP with a profound decrease in bone mineralization leading to excess circulating calcium and phosphorus. In cases where it is necessary to interrupt ERT, we advise close monitoring of calcium and phosphorous levels.
Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: ND is on the speaker bureau for Alexion and has been a consultant for them in the past.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
1. Whyte, M, Leung, E, Wilcox, W, Liese, J, Argente, J, Martos-Moreno, GÁ, et al.. Natural history of perinatal and infantile hypophosphatasia: a retrospective study. J Pediatr 2019;209:116–24. https://doi.org/10.1016/j.jpeds.2019.01.049.Search in Google Scholar
2. Whyte, M, Rockman-Greenberg, C, Ozono, K, Riese, R, Moseley, S, Thrompson, D, et al.. Asfotase alfa treatment improves survival for perinatal and infantile hypophosphatasia. J Clin Endocrinol Metab 2016;101:334–42. https://doi.org/10.1210/jc.2015-3462.Search in Google Scholar
3. Hofmann, C, Harmatz, P, Vockley, J, Högler, W, Nakayama, H, Bishop, N, et al.. Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study. J Clin Endocrinol Metab 2019;104:2735–47. https://doi.org/10.1210/jc.2018-02335.Search in Google Scholar
4. Whyte, M, Simmons, J, Moseley, S, Fujita, K, Bishop, N, Salman, N, et al.. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol 2019;7:93–105. https://doi.org/10.1016/s2213-8587(18)30307-3.Search in Google Scholar
5. Mulder, M, Fawzy, I, Lance, M. ECMO and anticoagulation: a comprehensive review. Neth J Crit Care 2018;26:6–13.Search in Google Scholar
6. Pan, W, Pradhan, R, Pelto, R, Seefried, L. Pharmacokinetics of asfotase alfa in adult patients with pediatric-onset hypophosphatasia. J Clin Pharmacol 2021;61:1334–43. https://doi.org/10.1002/jcph.1870.Search in Google Scholar PubMed PubMed Central
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