Clinical Characteristics of Persistent Hypophosphatasemia Uncovered in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital

<b>Background:</b> Hypophosphatasemia is often overlooked despite its potential to indicate underlying pathologies. The aim of this study was to determine the prevalence of persistent hypophosphatasemia in a large, urban, multi-specialty hospital population and characterize the clinical and laboratory findings in adult patients with this condition. <b>Methods:</b> In this retrospective observational study, the results of 424,434 alkaline phosphatase (ALP) tests in 50,136 patients aged ≥18 years that were performed at Okayama University Hospital between July 2020 and October 2023 were analyzed. Persistent hypophosphatasemia was defined as consistently low ALP levels (≤40 IU/L) for 28 days with a minimum recorded level of ≤35 IU/L. <b>Results:</b> Persistent hypophosphatasemia was detected in 273 patients (0.54% of the tested patients), and the patients with persistent hypophosphatasemia included a higher proportion of females (72.5% vs. 52.9% in the people without persistent hypophosphatasemia; chi-squared test, <i>p</i> < 0.01) and had a younger median age (51 years vs. 63 years; Mann-Whitney U test, <i>p</i> < 0.01) than those in the overall tested population. The common causes of persistent hypophosphatasemia were cancer (30%), glucocorticoid use (21%), and immunosuppressants (16%). Notably, 38 patients (14%) had no apparent cause for low ALP values. These patients were categorized on the basis of their clinical characteristics, with some patients presenting symptoms potentially related to adult hypophosphatasia. <b>Conclusions:</b> This study provides prevalence and insights into the causes and characteristics of persistent hypophosphatasemia in a Japanese tertiary care setting. While most cases were associated with known causes, patients with unexplained hypophosphatasemia and symptoms such as chronic pain, muscle weakness, and general fatigue could have adult hypophosphatasia. In such cases, comprehensive evaluation and further investigation for hypophosphatasia should be considered. Persistent hypophosphatasemia of undetermined etiology could be a crucial initial step in diagnostic algorithms for this condition.