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Hypophosphatasia: From Diagnosis to Treatment

  • Orphan Diseases (Bernhard Manger, Section Editor)
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Abstract

Purpose of Review

Hypophosphatasia (HPP) is a rare genetic disorder caused by mutations of the ALPL gene. ALPL encodes the tissue-non-specific isoenzyme of alkaline phosphatase (TNSALP). Consequently, bone mineralization is decreased leading to fractures, arthralgia, and extra-skeletal manifestations including tissue calcification, respiratory failure, and neurological complications. This review summarizes the most important clinical findings, diagnosis, and treatment options for HPP.

Recent Findings

Asfotase alfa is a recombinant human alkaline phosphatase, used as treatment for the underlying cause of HPP. Asfotase alfa enhances the survival in life-threatening HPP and improves bone mineralization, muscle strength, and pulmonary function. However, discontinuation of asfotase alfa leads to reappearance of bone hypomineralization.

Summary

Due to its varied manifestations, HPP often mimics rheumatological and other bone diseases, thereby delaying its diagnosis. Asfotase alfa, a recombinant alkaline phosphatase, is available for the long-term enzyme replacement therapy in patients with pediatric-onset HPP to treat the bone manifestations of the disease.

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Authors and Affiliations

  1. 1st Medical Department, Hanusch Hospital, Heinrich Collin-Str. 30, 1140, Vienna, Austria

    Sebastian Simon, Klaus Klaushofer, Jochen Zwerina & Roland Kocijan

  2. St. Vincent Hospital – Academic Teaching Hospital of the Medical University of Vienna, Vienna, Austria

    Heinrich Resch

  3. Medical Faculty of Bone Diseases, Sigmund Freud University, Vienna, Austria

    Heinrich Resch

  4. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, Vienna, Austria

    Klaus Klaushofer, Paul Roschger, Jochen Zwerina & Roland Kocijan

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Roland Kocijan and Heinrich Resch reports grants from ALEXION, outside the submitted work and speaker honoraria from ALEXION.

Sebastian Simon, Klaus Klaushofer, Paul Roschger, and Jochen Zwerina declare that they have no conflict of interest.

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Simon, S., Resch, H., Klaushofer, K. et al. Hypophosphatasia: From Diagnosis to Treatment. Curr Rheumatol Rep 20, 69 (2018). https://doi.org/10.1007/s11926-018-0778-5

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