Hypophosphatasia in adolescents and adults:​ overview of diagnosis and treatment

Bianchi, M. L.<sup>1</sup>; Bishop, N. J.<sup>2</sup>; Guañabens, N.<sup>3</sup>; Hofmann, C.<sup>4</sup>; Jakob, F.<sup>5</sup>; Roux, C.<sup>6</sup>; Zillikens, M. C.<sup>7</sup>

Affiliations

¹Laboratorio sperimentale di ricerche sul metabolismo osseo infantile, Centro Malattie Metaboliche Ossee, Istituto Auxologico Italiano IRCCS, Milan, Italy

²Department of Oncology and Metabolism, University of Sheffield, Sheffield Children’s NHS Foundation Trust, Sheffield, UK

³Servicio de Reumatología, Hospital Clínic, Universidad de Barcelona, IDIBAPS CIBERehd, Barcelona, Spain

⁴Children’s Hospital, University of Würzburg, Würzburg, Germany

⁵Orthopedic Centre for Musculoskeletal Research, University of Würzburg, Würzburg, Germany

⁶INSERM U1153 APHP Centre, Université de Paris, Department of Rheumatology, Paris, France

⁷Department of Internal Medicine, Endocrinology Section, Erasmus Medical Centre, Rotterdam, The Netherlands

Abstract and keywords

This article provides an overview of the current knowledge on hypophosphatasia—a rare genetic disease of very variable presentation and severity—with a special focus on adolescents and adults. It summarizes the available information on the many known mutations of tissue-nonspecific alkaline phosphatase (TNSALP), the epidemiology and clinical presentation of the disease in adolescents and adults, and the essential diagnostic clues. The last section reviews the therapeutic approaches, including recent reports on enzyme replacement therapy (EnzRT).

Keywords: Alkaline phosphatase; Bone; Fractures; Hypomineralization; Hypophosphatasia; Teeth

Links

DOI: 10.1007/s00198-020-05345-9

PubMed: 32162014

WoS: 000548231300004

History

Received: 2019-07-22

Accepted: 2020-02-11

Online: 2020-03-11

Cited Works (6)

Year	Entry
2016	Whyte MP. Hypophosphatasia: aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. April 2016;12(4):233-246.
2013	Berkseth KE, Tebben PJ, Drake MT, Hefferan TE, Jewison DE, Wermers RA. Clinical spectrum of hypophosphatasia diagnosed in adults. Bone. May 2013;54(1):21-27.
2014	Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O’Keefe R, Papapoulos S, Howe TS, van der Meulen MCH, Weinstein RS, Whyte MP. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. January 2014;29(1):1-23.
2017	Schmidt T, Mussawy H, Rolvien T, Hawellek T, Hubert J, Rüther W, Amling M, Barvencik F. Clinical, radiographic and biochemical characteristics of adult hypophosphatasia. Osteoporos Int. September 2017;28(9):2653-2662.
2017	Whyte MP. Hypophosphatasia: an overview for 2017. Bone. September 2017;102:15-25.
2014	McKiernan FE, Berg RL, Fuehrer J. Clinical and radiographic findings in adults with persistent hypophosphatasemia. J Bone Miner Res. July 2014;29(7):1651-1660.

Cited By (2)

Year	Entry
2021	Desborough R, Nicklin P, Gossiel F, Balasubramanian M, Walsh JS, Petryk A, Teynor M, Eastell R. Clinical and biochemical characteristics of adults with hypophosphatasia attending a metabolic bone clinic. Bone. March 2021;144:115795.
2022	Costantini A, Mäkitie RE, Hartmann MA, Fratzl-Zelman N, Zillikens MC, Kornak U, Søe K, Mäkitie O. Early-onset osteoporosis: rare monogenic forms elucidate the complexity of disease pathogenesis beyond type I collagen. J Bone Miner Res. September 2022;37(9):1623-1641.