Hypophosphatasia: current concepts in diagnosis and management of a rare metabolic disorder

Vollständiger Abstract

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Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by deficient activity of tissue non-specific alkaline phosphatase (TNSALP). The resulting accumulation of its substrates, particularly inorganic pyrophosphate (PPi) and pyridoxal-5-phosphate (PLP), impairs skeletal and dental mineralization and disrupts vitamin B6 metabolism, contributing to multisystem manifestations. The clinical spectrum is highly heterogeneous, ranging from severe, life-threatening forms in the perinatal period to milder musculoskeletal and dental phenotypes presenting in adulthood. The rarity of HPP, together with the nonspecific nature of many symptoms, contributes to frequent diagnostic delay. However, recognition of characteristic biochemical abnormalities and clinical features can facilitate earlier identification and appropriate management. This review summarizes current evidence regarding the pathophysiology, clinical manifestations, diagnosis, and management of HPP, with particular emphasis on diagnostic challenges, biomarker interpretation, and recent advances in patient care.