Box 1.

Proposed asfotase alfa treatment initiation and monitoring guide for hospitalized patients with a confirmed diagnosis of life-threatening HPP.

1.Treatment initiation phase: □Central access □Baseline laboratory investigations: ionized calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), pyridoxal-5-phosphate (PLP), liver function, & renal function (blood); calcium & creatinine (urine) □Skeletal survey (if not already done) □Baseline renal ultrasound □Baseline eye exam □Hearing screen □Education of the primary care team (including bedside nursing and allied health professionals) about the disease and the treatment, including potential complications and outcomes □Consultation with relevant medical subspecialties (e.g., Medical Genetics, Endocrinology, Respirology, Neurology, Orthopaedics) 2.Treatment monitoring phase: Daily*: □Assessment of respiratory support needs (if applicable) □Assessment of sedation and analgesia requirements (if applicable) □Bedside nurse subjective impression of response to handling Twice weekly*: □Laboratory investigations: ionized calcium, phosphate, ALP, & PTH (blood) □Weight Weekly*: □Head circumference and length □Nutritional review □Laboratory investigations: calcium & creatinine (urine) □Scheduled family meeting □Team meeting to review treatment course, evidence of response/non-response, and drug dosing Every two weeks*: □Chest x-ray □Pulmonary function testing (if possible) Monthly*: □Eye exam for increased intracranial pressure and calcium deposition □Renal ultrasound for nephrocalcinosis □Multidisciplinary meeting to review treatment course and evidence of response/non-response □Unified recommendation regarding continuation of therapy As needed: □STAT ionized calcium level, treatment with pyridoxine, and standard-of-care investigations and treatment, for seizures □Standard-of-care investigations and treatment, including consideration of gastrostomy tube, for feeding difficulties □Craniofacial CT scan (low dose - bone only), for craniosynostosis and related complications □Consultation with hospital bioethicist *And as needed