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.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.
Maheshwari et al. (Tue,) studied this question.