A Rare Case Presentation of Hypophosphatasia - Bone Pain and Mild Fatigue in a 79-Year-Old Male

Sep 29, 2026

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Hypophosphatasia (HPP) is an uncommon metabolic bone disorder caused by ALPL gene mutations, characterized by reduced alkaline phosphatase (ALP). Adult HPP can imitate rheumatologic diseases, complicating diagnosis when symptoms are mild. This case describes a 79-year-old man with mild bone pain and fatigue, persistently low ALP, and elevated pyridoxal-5-phosphate (vitamin B6), with radiographs showing no significant findings. Asfotase alfa was recommended and genetic testing advised.

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Abstract

Introduction

Definition and diagnostic criteria

Epidemiology and inheritance

Clinical manifestations

Case presentation and evaluation

EuropeanJournalof Rheumatology DOI: 10. 5152/eurjrheum.2025.24094 Case Report A Rare Case Presentation of Hypophosphatasia: Bone Pain and Mild Fatigue in a 79-Year-Old Male Karan Kumar Maheshwari, Mashal Maheshwari, Muhammad Shehryar, Hira Khalid Kareem, Issac Sachmechi ORCID iDs of the authors: K. K.M. 0009-0008-2411-261X; M.M. 0009-0003-4503-9646; M.S. 0000-0001-8837-1751; H. K. K. 0000-0001-5279-4998; I. S. 0000-0003-2893-780X. Cite this article as: Maheshwari KK, Maheshwari M, Shehryar M, Kareem HK, Sachmechi I. A rare case presentation of hypophosphatasia: bone pain and mild fatigue in a 79-year-old male. Eur J Rheumatol. 2025, 12(3), 0094, doi: 10. 5152/eurjrheum.2025.24094. Division of Endocrinology, Department of Internal Medicine, Queens Hospital Center Ichan School of Medicine, New York, USA Corresponding author: Karan Kumar Maheshwari E-mail: [kkl.1998@yahoo.com](kkl.1998@yahoo.com) [Received: October 30](Received: October 30), 2024 Revision Requested: February 14, 2025 Last Revision Received: March 4, 2025 Accepted: April 15, 2025 Publication Date: September 17, 2025 Copyright@Author(s) -Available online at [www.eurjrheumatol.org](www.eurjrheumatol.org). Content of this journal is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Abstract Hypophosphatasia (HPP) is an uncommon metabolic bone condition resulting from mutations in the ALPL gene and is defined by reduced levels of alkaline phosphatase (ALP) . It presents in various forms ranging from severe perinatal cases to milder adult-onset forms. Adult HPP often mimics rheumatologic diseases, making diagnosis challenging, especially with mild symptoms. The case of a 79-year-old man who came in with symptoms of mild bone pain and fatigue is presented. His medical history included pre-diabetes, hypertension, and vitamin D deficiency. Laboratory tests showed persistently low ALP and elevated pyridoxal-5-phosphate (Vitamin B6), suggesting HPP. No significant findings were observed on radiographs, and other causes such as hypermetabolic conditions were ruled out. The patient’s symptoms, along with consistently reduced ALP levels and increased Vitamin B6, confirmed a diagnosis of adult-onset HPP. Treatment using Asfotase alfa for the replacement of the enzyme was advised. His symptoms were mild, and no previous fractures, early tooth loss, or bone deformities were noted. This case underscores the significance of considering HPP in patients presenting with unexplained bone pain and fatigue, particularly when ALP levels are low. Early diagnosis can prevent inappropriate treatments and guide effective management, even in asymptomatic or mild cases. Further genetic testing and monitoring were recommended for this patient. Keywords: Alkaline phosphatase, hypophosphatasemia, hypophosphatasia, inorganic pyrophosphate, phosphoethanolamine, pyridoxal-5-phosphate Introduction Hypophosphatasia (HPP) is an uncommon metabolic bone condition caused by mutations in the ALPL gene, which codes for tissue-nonspecific alkaline phosphatase. This condition results in abnormally reduced levels of circulating alkaline phosphatase (ALP) known as hypophosphatasemia.1 Hypophosphatasia is diagnosed when either 2 major criteria are met—such as the presence of a pathogenic ALPL mutation, elevated levels of enzyme substrates (like pyridoxine), pseudofractures, or recurrent fractures of the metatarsals—or when one of these major criteria is accompanied by 2 minor criteria, including musculoskeletal, dental, and kidney-related symptoms in adults, along with neurological signs in children.2 The exact prevalence of hypophosphatasia remains unclear; however, 1 study guessed the occurrence of severe cases to be 1 out of 100 000 live births.3 Other research suggests that milder forms of the disease may occur more frequently.4 Approximately 1 in 200 people in the United States might be HPP carriers. Hypophosphatasia i

FAQs

What defines hypophosphatasia and how is it diagnosed in this report?

Hypophosphatasia is defined by reduced alkaline phosphatase activity due to ALPL gene mutations. Diagnosis in adults is supported by major and minor criteria, including pathogenic ALPL mutation and elevated enzyme substrates such as pyridoxine, along with musculoskeletal and related symptoms.

What key laboratory findings supported HPP in the 79-year-old male case?

Laboratory testing showed persistently low ALP and elevated pyridoxal-5-phosphate (vitamin B6). Radiographs did not show significant findings, and other causes were ruled out.

What treatment was advised for the patient and what was the clinical significance of early diagnosis?

Asfotase alfa was recommended to replace the deficient enzyme. The case highlights that considering HPP in patients with unexplained bone pain and fatigue—especially when ALP is low—can prevent inappropriate treatments and support effective management even in mild cases.

Sep 29, 2026

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