Introduction: Persistent hypophosphatasia (pHPE) can be an expression of hypophosphatasia (HPP), a rare disorder of bone metabolism resulting from ALPL gene pathogenic variants. The aim of this study was to identify the role of auxiliary general biomarkers to verify low ALP serum activity as an alert parameter for an ALPL gene pathogenic variants. Material: A retrospective analysis of adult patients with at least one reduced ALP value of less than 21 U/L was performed. 88 patients had a temporary HPE (tHPE group). 12 out of 20 patients with persistent HPE agreed to a genetic analysis. 11 patients had a pathogenic ALPL gene variant (ALPL group). Hemoglobin [HB], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], calcium, phosphate, thyrotropin [TSH], albumin, total protein, and C-reactive protein [CRP] levels) represented basic biomarkers. A statistical comparison of general biomarkers was performed between both groups. Results: The mean HB, ALP, AST, calcium, albumin, and total protein levels were lower in the tHPE group (p