ECTS2014 Poster Presentations Other diseases of bone and mineral metabolism (44 abstracts)
Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms
Michael Whyte 1 , Edward Leung 2 , William Wilcox 3 , Johannes Liese 4 , Amy Reeves 1 , Agustin Melian 5 , Tatjana Odrljin 6 , Hui Zhang 6 & Christine Hofmann 4
1Shriner’s Hospital for Children, St Louis, MO, USA; 2University of Manitoba, Winnipeg, MB, Canada; 3Cedars-Sinai Medical Center,
Los Angeles, California, USA; 4University Children's Hospital, University of Würzburg, Würzburg, Germany; 5Alexion Pharmaceuticals, Cheshire, Connecticut, USA; 6Alexion Pharmaceuticals, Cambridge, Massachusetts, USA.
Background: Hypophosphatasia (HPP) is caused by inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase. Extracellular accumulation of inorganic pyrophosphate can lead to profound hypomineralization resulting in limb and chest deformity, respiratory complications and vitamin B6-dependent seizures in the severe forms of HPP. The natural history of HPP is poorly understood, but the perinatal and infantile forms are often considered lethal.
Objective: To clarify the natural history of perinatal and infantile HPP.
Methods: This was a multicentre, multinational, retrospective chart review study of patients (pts) with perinatal or infantile HPP (onset <6 months of age) with at least one of the following features: respiratory complications, rachitic chest deformity or seizures. Data collection spanned the first 5 years of age. The primary and secondary outcome evaluations were survival and invasive ventilator-free survival, respectively.
Results: 48 pts were eligible, 14 of whom had signs of HPP in utero. At the time of diagnosis (median age 8.6 weeks), 32/48 patients (67%) had radiographic evidence of rachitic chest deformity. At the time of our study, 13 (27%) patients were alive (median age: 7.7 years (range: 1.6–19.7 year)); 35 (73%) patients had died (median time to death 8.9 months (95% CI: 5.1–14.1)), with a 31 and 58% probability of death by 3 and 12 months respectively. All ten patients with seizures died. Respiratory support was required for 29 patients; of these, 19 required invasive ventilation, with a median time to invasive ventilation or death of 7.8 months (95% CI: 2.6–9.9). Nearly 50% of the infants requiring respiratory support received maximal respiratory support within the first 6 days of life. Among the 13 patients alive at the time of chart review, three had received respiratory support and one of these had required invasive ventilation.
Conclusion: Perinatal or infantile HPP complicated by respiratory compromise, seizures or chest deformity is associated with high mortality.
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