Prevalence of hypophosphatasia in adult patients in rheumatology

Background Hypophosphatasia (HPP) is a genetic disorder caused by one or more mutations in the alkaline phosphatase (ALP) gene, responsible for encoding tissue-specific ALP and for the mineralization process. Objective Identification of the prevalence of HPP in rheumatology patients. Material and methods Medical records of all adult rheumatology patients with pathologically low total ALP levels (<35 U/L) treated in the Department of Rheumatology at the Clinic of Internal Medicine III, University Hospital Bonn between January 2017 and June 2019, were retrospectively examined for clinical signs as well as for results of genetic tests for HPP. Results In 60 out of 2289 patients (2.62%) pathologically low ALP levels were detected. Of these 30 (1.31%) were found to have persistently low ALP levels. Genetic testing for ALP gene mutations was performed in 19 of these 30 patients and 7 of the 19 patients (36.84%) had HPP signs (insufficiency fractures, or bad dental status since childhood), all with pathologic ALP mutations. Of these patients 3 (15.78%) each had a history of insufficiency fracture with normal bone densitometry. Overall, 13 out of the 19 patients (68.42%) had mutations in the ALP gene. Interestingly, no association with chondrocalcinosis was detected in any of the patients. Conclusion The HPP seems to be an underdiagnosed disease with a higher proportion of affected rheumatology patients. Therefore, future studies should aim to develop a diagnostic protocol in the clinical practice.