Osteoporosis.

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Abstract

[Indexed for MEDLINE] 9. J Bone Miner Res. 2024 Jul 23;39(6):655-660. doi: 10.1093/jbmr/zjae098. Pediatric hypophosphatasia: avoid diagnosis missteps! Whyte MP(1)(2), McAlister WH(3), Mack KE(2), Mumm S(1)(2), Madson KL(2). Author information: (1)Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital; St. Louis, MO 63110, United States. (2)Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children-St. Louis; St. Louis, MO 63110, United States. (3)Pediatric Radiology Section, Mallinckrodt Institute of Radiology at St. Louis Children's Hospital, Washington University School of Medicine; St. Louis, MO 63110, United States. Hypophosphatasia (HPP) is the dento-osseous disorder caused by deactivating mutation(s) of ALPL, the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). In HPP, 3 natural substrates of cell-surface TNSALP accumulate extracellularly; phosphoethanolamine (PEA), inorganic pyrophosphate (PPi), and pyridoxal 5'-phosphate (PLP). Hypophosphatasemia together with elevated plasma levels of PEA, PPi, and PLP comprise its biochemical signature. PPi can inhibit mineralization and in extracellular excess can impair bone and tooth hardening and perhaps explain weak muscle. Autosomal dominant or autosomal recessive inheritance from among more than 400 mutations of ALPL largely accounts for HPP's broad-ranging severity, greatest among all skeletal diseases. Pediatric HPP spans life-threatening perinatal and infantile forms, childhood forms, and odonto-HPP selectively featuring premature loss of deciduous teeth. ALPL gene testing and TNSALP supplementation therapy have bolstered familiarity with HPP, but there are new considerations for diagnosis. Herein, diagnosis of a boy's mild childhood HPP was delayed by missteps involving his medical and dental history, physical examination, radiographic findings, and clinical laboratory studies. We review how pediatric HPP is now identified. Prompt diagnosis while appreciating the broad-ranging severity of HPP underlies the safe and effective management of this inborn-error-of-metabolism. © The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com. DOI: 10.1093/jbmr/zjae098