Abstract
BackgroundHypophosphatasia (HPP) is a rare, inherited, metabolic bone disease caused by deficient tissue-non-specific isoenzyme of alkaline phosphatase activity that manifests as a broad range of signs/symptoms, including bone mineralization defects and systemic complications. The burden of disease is poorly characterized, particularly in children. This study aimed to characterize the patient-reported burden of disease among children with HPP using two survey instruments: the HPP Impact Patient Survey (HIPS) and the HPP Outcomes Study Telephone interview (HOST).MethodsBetween September 2009 and June 2011, pediatric patients (aged younger than 18 years) with HPP were recruited to participate in the study via patient advocacy groups or their medical provider. Survey questions were used to capture information on patient demographics, HPP-related medical history, mobility, and health-related quality of life (HRQoL; using the 10-item Short-Form Health Survey for Children [SF-10], HIPS only).ResultsCommon clinical features of the 59 pediatric survey respondents (mean [standard deviation] age: 7.6 [5.1] years; 51% male) included pain (86% of patients), muscle weakness (71%), difficulty gaining weight (64%), and delayed walking (59%). Fracture was reported by 36% of patients; multiple fractures were also reported (15% of patients). Use of assistive devices for mobility was frequent among the study population (51%). In response to the SF-10, patients reported a substantial impact of HPP on their HRQoL; physical function was the most severely impaired component relative to normative data. Of patients responding to the HOST, two-thirds experienced worsening of at least one of their HPP-related signs/symptoms over a 5-year period.ConclusionsIn pediatric patients, HPP is associated with a high burden of disease and a substantial negative impact on HRQoL. The burden of HPP may increase and HRQoL reduce further over time as signs/symptoms that affect HRQoL worsen or new signs/symptoms manifest.
Highlights
Hypophosphatasia (HPP) is a rare, inherited, metabolic bone disease caused by deficient tissue-nonspecific isoenzyme of alkaline phosphatase activity that manifests as a broad range of signs/symptoms, including bone mineralization defects and systemic complications
PPi is a potent inhibitor of bone mineralization [2]; in HPP, excess PPi contributes to skeletal hypomineralization, which can result in the premature loss of deciduous teeth, HPP-related rickets in infants and children, and osteomalacia in patients of any age [3]
Mortality is high among those who present with HPP in the perinatal and infantile periods [1]; it is recognized that significant complications associated with HPP can occur at any age, and that those individuals who survive infancy or who present with HPP-related manifestations after infancy often experience a high disease burden [7]
Summary
Hypophosphatasia (HPP) is a rare, inherited, metabolic bone disease caused by deficient tissue-nonspecific isoenzyme of alkaline phosphatase activity that manifests as a broad range of signs/symptoms, including bone mineralization defects and systemic complications. Mortality is high among those who present with HPP in the perinatal and infantile periods [1]; it is recognized that significant complications associated with HPP can occur at any age, and that those individuals who survive infancy or who present with HPP-related manifestations after infancy often experience a high disease burden [7] These manifestations of HPP are often debilitating and frequently include poor growth [7,8,9,10], delayed motor milestones [9, 11], muscle weakness [7, 10], gait abnormalities, chronic bone, muscle and/or joint pain [12, 13], dental abnormalities [14], and recurrent low trauma fractures [7, 15]. Individuals with HPP frequently experience a diminished health-related quality of life (HRQoL) [7]
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