Bone Abstracts

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Resultant low TNSALP leads to defective skeletal mineralization and diverse complications that may include poor growth, proximal muscle weakness, pain, and compromised physical function in children. Here, we describe the burden of HPP in patients <18 years old as assessed by two surveys specific to HPP symptomology.

Methods: The Hypophosphatasia Impact Patient Survey (HIPS, internet-based) and the Hypophosphatasia Outcomes Study Telephone interview (HOST) were developed to characterize the burden of disease in patients with HPP. Answers consisted of yes/no, ‘check all that apply,’ and free text fields. Outreach from 2009–2011 by patient advocacy groups (HIPS, HOST) or physicians (HOST) provided awareness of the survey to patients or caregivers and invited participation. Data from questions common to both surveys were pooled for analysis. Results are expressed as percentage of patients who responded to each item.

Results: 59 children (51% male; 75% caregiver responders) participated in the surveys (HIPS n=44; HOST n=15). Mean (standard deviation (S.D.)) age at survey was 7.6 (5.1) years; age at HPP onset was 0.8 (0.9) years. Skeletal abnormalities included abnormally shaped chest (54%, 32/59) and head (53%; 30/57), genu valgum (39%, 23/59) and genu varum (37%, 22/59). 42% (25/59) reported past fracture; 15% (9/59) reported >1 fracture. Muscle weakness (71%, 41/58), delayed walking (59%, 34/58), and unusual gait (57%, 25/44; HIPS only) were common. Pain (86%, 51/59) and recent pain (71%, 42/59) were prevalent. 51% (30/59) of children had required an assistive device at some point. At the time of survey, 38% (20/53) required a wheelchair, and 25% (13/53) required walking devices. In HOST, 73% (11/15) children reported difficulty climbing and descending stairs, and 12/12 children reported difficulty jumping. In HIPS, children reported using outpatient health services including physical (36%, 16/44) and occupational (23%, 10/44) therapy.

Conclusions: These patient/caregiver-reported data suggest children with HPP experience a high burden of disease and substantial morbidity that limits activities of daily living and quality of life. Additional studies are needed to fully elucidate the impact of HPP in children.

Disclosure: Scott Moseley, Eileen K Sawyer, and Tatjana Odrljin are employees of Alexion Pharmaceuticals, Inc., which funded and analyzed the HIPS and HOST studies.

Thomas J Weber has received consulting fees from Alexion Pharmaceuticals, Inc.

Priya S Kishnani has received honoraria from Alexion Pharmaceuticals, Inc and is chair of the HPP registry board.

Editorial support was provided by Fishawack Communications, GmbH, Basel, Switzerland, a member of the Fishawack Group of Companies, and was funded by Alexion Pharmaceuticals, Inc.