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Massive calcification around large joints in a patient subsequently diagnosed with adult-onset hypophosphatasia

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Abstract

We report a 64-year-old Japanese woman with a history of progressive loss of motor function and painful swelling of large joints. At the age of 54, profound calcification appeared around the shoulder and hip joints, which did not heal after repeated surgical resections. Iliac bone biopsy revealed osteomalacic changes. Laboratory data showed low serum alkaline phosphatase (ALP) activity and a high urine phosphoethanolamine (PEA) concentration with normal serum calcium, phosphate, and fibroblast growth factor 23 (FGF23) levels. Subsequent genetic analysis of the ALPL gene confirmed the diagnosis of hypophosphatasia (HPP) with the identification of a heterozygous single nucleotide deletion, c.1559delT (p.Leu520ArgfsX86). We started a mineral-targeted enzyme replacement therapy, asfotase alfa (AA), to treat the patient’s musculoskeletal symptoms. A follow-up bone biopsy after 12 months of AA treatment showed improvement of osteomalacia. Calcified deposits around the large joints were unchanged radiographically. To our knowledge, this is the first report of a patient with an adult-onset HPP who presented with profound calcification around multiple joints. Nonspecific clinical signs and symptoms in patients with adult-onset HPP often result in delayed diagnosis or misdiagnosis. We propose that bone biopsy and genetic analysis should be considered along with laboratory analysis for all patients with ectopic calcification around joints of unknown etiology for accurate diagnosis and better treatment.

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Funding

This study was supported by JSPS KAKENHI Grant Number 18K09018.

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Authors and Affiliations

  1. Division of Nephrology and Endocrinology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    M. Koga, Y. Kinoshita, H. Kato, M. Nangaku, N. Makita & N. Ito

  2. Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo, Japan

    H. Kobayashi

  3. Department of Rehabilitation Medicine, The University of Tokyo Hospital, Tokyo, Japan

    Y. Shinoda

  4. Vanderbilt University Medical Center, Program for Metabolic Bone Disorders, Nashville, TN, USA

    K. M. Dahir

Authors
  1. M. Koga
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  2. Y. Kinoshita
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  3. H. Kato
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  4. H. Kobayashi
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  5. Y. Shinoda
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  6. M. Nangaku
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  7. N. Makita
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  8. K. M. Dahir
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  9. N. Ito
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Corresponding author

Correspondence to N. Ito.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required. The study protocols were approved by the institutional review board of the University of Tokyo (approval number: G10115).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

Kathryn M Dahir is a clinical trial investigator and a consultant for Alexion pharmaceuticals. Minae Koga, Yuka Kinoshita, Hajime Kato, Hiroshi Kobayashi, Yusuke Shinoda, Masaomi Nangaku, Noriko Makita, and Nobuaki Ito declare that they have no conflict of interest.

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Koga, M., Kinoshita, Y., Kato, H. et al. Massive calcification around large joints in a patient subsequently diagnosed with adult-onset hypophosphatasia. Osteoporos Int 33, 505–509 (2022). https://doi.org/10.1007/s00198-021-06145-5

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  • DOI: https://doi.org/10.1007/s00198-021-06145-5

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