Search

Objective: To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia. Study design: Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age 70% of patients between birth and age 5 years. Vitamin B6–dependent seizures and respiratory distress and failure were associated significantly (P

PURPOSE: To modify the Performance-Oriented Mobility Assessment-Gait (POMA-G) subtest and validate this modified POMA-G (mPOMA-G) in children with hypophosphatasia (HPP), a rare metabolic disorder that can manifest with musculoskeletal symptoms that impair mobility and ambulation. METHODS: Based on feedback from an expert panel, the POMA-G was modified by removing gait initiation/path assessments and expanding the rating scale for step length/continuity to capture aspects of observational gait analysis relevant to children with HPP. Three trained physical therapists used the mPOMA-G for video-based assessments of gait in 14 children with childhood HPP who participated in a clinical study of asfotase alfa or in a natural history study. Intraclass correlation coefficients (ICCs) were calculated to determine interrater and intrarater agreement. Concurrent validity was evaluated by correlations with other validated assessment tools. RESULTS: Across 192 observations from available videos, interrater and intrarater agreement of mPOMA-G scores was significant (ICCs: 0.76 for both; P< 0.001). mPOMA-G scores had strong concurrent validity with the Childhood Health Assessment Questionnaire, Pediatric Outcomes Data Collection Instrument Transfer and Mobility Scale, Sports and Physical Function subscale, and 6-Minute Walk Test (all P⩽ 0.0002). CONCLUSION: The mPOMA-G is a reliable and valid measure for detecting clinically significant impairments in children with HPP.

Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy of asfotase alfa therapy for the life-threatening perinatal and infantile forms of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa treatment administered to children 6-12 years of age at baseline who were substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal disease, including comparisons to serial radiographs from similarly affected historical control patients. Results. Twelve children receiving treatment were studied for 5 years. The 6-month primary endpoint was met, showing significant radiographic improvement. Additional significant improvements included patient growth, strength, motor function, agility, and quality of life, which for most patients meant achieving normal values for age- and sex-matched peers that were sustained at 5 years of treatment. For most, pain and disability resolved. Mild to moderate injection-site reactions were common and were sometimes associated with lipohypertrophy. Low anti-asfotase alfa antibody titers were noted in all patients. No evidence emerged for clinically important ectopic calcification or treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has substantial and sustained efficacy with a good safety profile for children suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484 (https://clinicaltrials.gov/ct2/show/NCT00952484) and NCT01203826 (https://clinicaltrials.gov/ct2/show/NCT01203826). Funding. Alexion Pharmaceuticals Inc. and Shriners Hospitals for Children.

Occupational health nurses are in the unique position to influence health in the work force. To maximize this positive health influence, occupational health nurses should develop the skills of emotional intelligence. Emotional intelligence includes awareness of self and others and empathy. These behaviors are congruent with the mission of nursing because they improve health outcomes. Occupational health nurses who are emotionally intelligent have improved relationships with others, an important aspect of the nursing role. Emotional intelligence can be developed. The process begins with self-awareness, enhanced through self-care behaviors, such as exercise and journaling. Reading popular self-help literature also can improve self-awareness. After a nurse becomes self-aware, the next phase is to develop an awareness of others. This can be learned using the same type of techniques in the self-awareness stage. The final step is the development of empathy. This is the active step using the knowledge developed in the prior two stages. Through discipline and effort, an individual can learn to actively listen to others. This type of listening fosters empathy. By working in a positive, caring environment, personal growth in emotional intelligence can be enhanced (McMullen, 2003). Through the development of emotional intelligence, the nurse can improve personally and professionally, a win-win situation for all involved.

Hypophosphatasia (HPP), a heritable metabolic bone disease, results from inactivating mutation(s) in the gene for the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). The natural substrates that accumulate in HPP include inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5′ phosphate (PLP), the principal circulating form of vitamin B6. PPi excess blocks hydroxyapatite crystal formation causing rickets in growing children and osteomalacia in adults. There is no approved therapy. ENB-0040, a bone-targeted, recombinant, human TNSALP given subcutaneously has improved severely affected infants and children with HPP. Objective: Evaluate TNSALP substrate levels following 24 weeks of ENB-0040 treatment (Rx) and six-minute walk test (6MWT) function in adolescents and adults with HPP. The 6MWT is a performance-based measure of functional exercise capacity. Methods: 6 adolescents and 13 adults with HPP (mean age 42 yrs [14–68]) were randomized in an open-label, multicenter, multinational, dose-ranging, concurrent control study of the safety, efficacy, and pharmacokinetics of ENB-0040. Patients received 0, 2.1, or 3.5 mg/kg/wk of ENB-0040. Results: At baseline (BL), patients averaged 349 m during the 6MWT (6–620 m), but 10 required assistive devices. The differences walked for the Rx vs no Rx groups were +26 vs −14 m at week 24. Among those with functional impairment (n=12) whose BL 6MWT was 25%N75% of normal, 9 improved (8/9 Rx, and 1/3 no Rx). The mean improvements for the 2.1 and 3.5 mg/kg/wk groups were +35.4 m (n=5) and +43.5 m (n=4), respectively. Injection site reactions occurred in 7 patients, but did not cause discontinuation of treatment. Six serious adverse events (SAEs) were reported among 3 patients, two observation patients had 4 of the SAEs. No SAEs were from ENB-0040. Serum PLP levels decreased in both groups, from 324 and 602 ng/mL at BL to 69 ng/mL and 38 ng/L at week 24, respectively (p=0.009). Conclusion: ENB-0040 significantly decreases TNSALP substrates and improves the 6MWT in adolescents and adults with HPP. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: M. Whyte grant/research support from Enobia, consulting fees from Enobia, C. Greenberg grant/research support from Enobia, Advisory Board Membership of Enobia, consulting fees from Enobia, P. Kishnani grant/research support from Enobia, Advisory Board Membership of Enobia, consulting fees from Enobia, K. Madson grant/research support from Enobia, A. Mhanni grant/research support from Enobia, T. Weber: none declared, K. Mack grant/research support from Enobia, A. Reeves grant/research support from Enobia, H. Plotkin employee of Enobia, N. Kreher employee of Enobia, H. Landy employee of Enobia. doi:10.1016/j.bone.2012.02.101 OC31 (recipient of a 2012 ECTS Travel Award) Detection of autoantibodies to osteoprotegerin in patients with severe idiopathic osteoporosis P. Riches⁎, T. Gilchrist, W.D. Fraser, S.H. Ralston Rheumatology Department, Institute of Genetics and Molecular Medicine, Edinburgh, UK Faculty of Medicine and Health Sciences, University of East Anglia