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Mol Genet Metab. 2017 Sep;122(1-2):4-17. doi: 10.1016/j.ymgme.2017.07.010. Epub 2017 Jul 25.

Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

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Division of Medical Genetics, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA(2).
Metabolic Bone Team, Sheffield Children's NHS Foundation Trust, Sheffield S10 2TH, UK.
Academic Unit of Child Health, University of Sheffield and Sheffield Children's Hospital, Sheffield S10 2TH, UK.
Division of Diabetes and Endocrinology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich NR4 7UY, UK.
Pediatric Gastroenterology and Nutrition, UCSF Benioff Children's Hospital Oakland, Oakland, CA 94609, USA.
Service d'Endocrinologie Pédiatrique, Hôpital Bicêtre Paris-Sud, APHP, 94270 Le Kremlin Bicêtre, France.
Paediatrics & Child Health, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
Division of Human Genetics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
Orthopedic Department, University of Würzburg, Würzburg, Bavaria 97074, Germany.
Department of Pediatrics, Osaka University, Suita, Osaka 565-0871, Japan.


Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical setting, and the clinician's professional judgment.


Alkaline phosphatase; Asfotase alfa; Enzyme replacement therapy; Hypophosphatasia; Metabolic bone diseases; Therapeutic drug monitoring; Tissue-nonspecific alkaline phosphatase

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