Do you see any of the following signs/ symptoms in neonates?1,2 Slender ribs and metaphyseal “tongues” of radiolucency (arrows) in the upper chest in a 3-week-old girl who died with Hypophosphatasia (HPP)1 Clinical Radiographic • Vitamin B6-responsive seizures • Shortening, bowing, and/or angulation • Respiratory insufficiency/failure of the long bones • Widened sutures and fontanelles • Small/narrow thorax • Osteochondral spurs (Bowdler spurs) • Fractures • Metaphyseal irregularities • Lucencies (“cupping” or “tongues”) • Thin ribs • Deficient/absent ossification of bones • Polyhydramnios Alexion® is a registered trademark of Alexion Pharmaceuticals, Inc. Copyright ©2019, Alexion Pharmaceuticals, Inc. All rights reserved. US/UNB-H/0033 HPP should be in your differential diagnosis1,2 • HPP is a progressive, systemic, inherited metabolic disorder2 • In HPP, a loss-of function mutation in the ALPL gene leads to deficient alkaline phosphatase (ALP) enzyme activity, the biochemical hallmark of HPP2 • ALP is an essential enzyme for bone mineralization; infants with HPP have poorly mineralized bones and usually require ventilatory support due to rachitic chest3 • Infants with HPP are critically ill and have a high mortality rate1 Skeletal Features That Can Differentiate HPP, OI, and ACG/HCG4 HPP OI Type II ACG/HCG Low bone density +++ +++ - Underossification of cranial vault +++ +++ + Unossified vertebral bodies Cervical and lumbosacral Thoracic - (typical location) (whole spine in ACG) Sharp demarcation between +++ - + (tapering) ossified and unossified vertebrae Fractures + +++ - Bowed legs ++ +++ + Shortened long bones Thin Broad Normal width Cupped metaphyses (Y shaped) +++ - + Osteochondral Bowdler spurs1,2 + - - Cleft palate - - ++ +++, very highly associated; ++, often associated; +, sometimes associated; -, not associated. HPP-differentiating features shown in yellow. ACG/HCG, achondrogenesis/hypochondrogenesis; OI, osteogenesis imperfecta. Additional considerations for diagnosis of HPP1 • Assess for low age- and sex-adjusted ALP activity in patients with suspicion of HPP1 • Normal range in infants younger than 14 days of age is 90 to 273 U/L5,a • Normal range in infants 15 days and younger than 1 year of age is 134 to 518 U/L5,a • Genetic testing for ALPL mutations is helpful in cases of diagnostic uncertainty and is essential for family genetic counseling1 aBased on Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER) data.5 EARLY DIAGNOSIS AND THE INVOLVEMENT OF A MULTIDISCIPLINARY TEAM MAY HELP PROVIDE THE BEST MANAGEMENT OPTIONS FOR INFANTS WITH HPP1 References: 1. Offiah AC, et al.Pediatr Radiol. 2019;49(1):3-22. 2. Rockman-Greenberg C. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388. 3. Bishop N. Clin Cases Miner Bone Metab. 2015;12(2):170-173. 4. Zankl A, et al. Am J Med Genet A. 2008;146A(9):1200-1204. 5. Colantonio DA, et al. Clin Chem. 2012;58(5):854-868. The information on this page is intended as educational information for healthcare professionals. It does not replace a healthcare professional’s judgment or clinical diagnosis. US/UNB-H/0033.