Gill AS, Sharma P, Nassar M, Marte E. Hypophosphatasia: A case report. World J Clin Cases 2025; 13(21): 103642 [DOI: 10.12998/wjcc.v13.i21.103642]
Corresponding Author of This Article
Mahmoud Nassar, MD, PhD, Postdoctoral Fellow, Department of Research, American Society for Inclusion, Diversity, and Equity in Healthcare, 705 Maple Road, Lewes, NY 19958, United States. nassarma@asidehealthcare.org
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Angad Singh Gill, Pallavi Sharma, Mahmoud Nassar, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14221, United States
Angad Singh Gill, Pallavi Sharma, Mahmoud Nassar, Erlin Marte, Department of Research, American Society for Inclusion, Diversity, and Equity in Healthcare, Lewes, DE 19958, United States
Erlin Marte, Department of Endocrinology, Buffalo Veterans Affairs Medical Center, Buffalo, NY 14215, United States
Author contributions: Gill AS, Sharma P, Nassar M, Marte E contributed equally to the conception, research, drafting, and critical revision of the work, and approved the final version to be published. They agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Informed consent statement: Obtained from the patient.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mahmoud Nassar, MD, PhD, Postdoctoral Fellow, Department of Research, American Society for Inclusion, Diversity, and Equity in Healthcare, 705 Maple Road, Lewes, NY 19958, United States. nassarma@asidehealthcare.org
Received: November 26, 2024 Revised: January 28, 2025 Accepted: March 27, 2025 Published online: July 26, 2025 Processing time: 152 Days and 16.1 Hours
Abstract
BACKGROUND
Hypophosphatasia (HPP) is a rare metabolic disorder caused by low tissue-nonspecific alkaline phosphatase (ALP) activity, presenting symptoms from bone demineralization to tooth loss. It affects multiple systems and is diagnosed based on clinical symptoms, radiological findings, and lab tests. This case report emphasizes considering HPP in patients with unexplained bone pain and low ALP levels, especially with underlying osteopenia or osteoporosis. It highlights the importance of genetic testing and counseling for early diagnosis and treatment, aiming to raise clinician awareness.
CASE SUMMARY
We present a case of a 65-year-old female patient who was referred to our endocrinology clinic for complaints of generalized bone pain and hypothyroidism. Initial evaluation revealed osteopenia, managed with calcium and vitamin D supplementation. Persistently low ALP levels and elevated vitamin B6 levels led to the diagnosis of HPP, confirmed by genetic testing identifying a pathogenic ALPL gene variant [c.119C>T (p.Ala40Val)]. Despite conservative treatment, her bone density declined, although remaining in the osteopenic range. The Fracture Risk Assessment score indicated a low risk of major osteoporotic and hip fractures, not warranting immediate treatment. Plans are underway to initiate enzyme replacement therapy with asfotase alfa.
CONCLUSION
Recognizing HPP is crucial, as early diagnosis and treatment can significantly improve patient outcomes and prevent complications.
Core Tip: This case report highlights the importance of considering hypophosphatasia (HPP) in patients with unexplained bone pain and low alkaline phosphatase levels, especially in the presence of osteopenia or osteoporosis. It underscores the role of genetic testing and counseling in diagnosing and managing HPP, emphasizing early identification and treatment to improve patient outcomes. The report also illustrates how HPP can explain multiple symptoms often misdiagnosed as conditions like fibromyalgia. Additionally, it aims to raise awareness about enzyme replacement therapies that can significantly improve quality of life and reduce complications for HPP patients.
