Bone Abstracts

Objectives: Hypophosphatasia (HPP) is the rare inherited metabolic disease caused by low tissue nonspecific alkaline phosphatase activity. HPP manifests a wide spectrum of complications, which may include HPP-related rickets and compromised physical function in children.

Methods: We report on clinical gait assessments based on archival video recordings of six children with onset of HPP symptoms at ≧6 months and documented HPP-related skeletal abnormalities enrolled in a retrospective non-interventional natural history study. Children with ≧2 clinical videos of basic mobility available between ages 5–15 years were eligible for inclusion in this sub-study. Gait performance was assessed using a version of the 12-point performance-oriented mobility assessment¹ modified to provide improved sensitivity for HPP-related impairments (MPOMA-G; 12=no impairment; 0=greatest impairment). A physical therapy descriptor checklist and chart review provided additional information on physical function. Data are reported as median (min, max).

Results: All six participants were boys from one study center; five had bowing of the long bones and all had gait disturbances. Age at first assessment (FA) and last assessment (LA) was 6.2 years (5.3, 10.7) and 11.1 years (8.2, 14.9) respectively. At FA, total MPOMA-G score was 6.0 (3.0, 11.0); all patients had trunk sway or compensatory patterns in the trunk or arms; five a steppage gait pattern, and four reduced step size and continuity. At LA, MPOMA-G was 7.5 (4.0, 11.0; change from FA: +1.5 (0.0,+2.0); P=0.0625) with no consistent pattern of change in any MPOMA-G component. At LA, four patients were unable to achieve a period-of-flight during running; all required self-support with a hand to transition from the floor to standing. Time standing on one foot (when data available) ranged from 1.5 to 5.6 sec, less than healthy peers.² Overall, proximal muscle weakness (deficits in hip muscle strength, positive Trendelenburg sign) was common.

Conclusions: These data demonstrate that children with HPP can have clinically significant and persistent gait impairments indicative of reduced balance and muscle strength. The burden of disease in such children compromises their community participation and activities of daily living.

Disclosure: Dawn Phillips received consulting fees from Alexion Pharmaceuticals, Inc.

Marc Vallee, Kenji P Fujita are the employees of Alexion Pharmaceuticals, Inc.

Katherine L. Madson has received honoraria from Alexion Pharmaceuticals, Inc.

Michael P. Whyte has received honoraria, research grants, and travel support from Alexion Pharmaceuticals, Inc.

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.

References

1. Tinetti ME. Am J Med. 1986.

2. Folio MR, Fewell RR. Pro-Ed 2000.