Regarding clinical features, all patients in the ALPL+ group reported a least one clinical sign, which can be related to HPP, and musculoskeletal pain was most strongly associated with a disease-causing variant in ALPL. Our data on clinical signs confirm that pain may be the most common symptom and burden in adult HPP (Högler et al., 2019; Weber et al., 2016). This evidence concerns the gene ALPL and hypophosphatasia.