Advancements in Understanding and Managing Hypophosphatasia: From Clinical Spectrum and Diagnosis to Therapeutic Strategies

Background: hypophosphatasia (hpp) is a rare, inherited metabolic disorder caused bymutations in the gene responsible for producing the tissue-nonspecific isoenzyme of alkalinephosphatase (tnsalp). the clinical spectrum of hpp ranges from severe, life-threateningforms in infants to milder forms in adults, primarily affecting dental health and bone integrity.objectives: this review aims to summarize the clinical manifestations and genetic underpinningsof hpp, discuss the diagnostic methodologies used to identify hpp and, highlight the therapeuticinterventions available, with a focus on recent advancements.results: the review synthesizes information from clinical observations, radiographic findings,laboratory tests, and genetic screenings. it also evaluates recent literature on the pathophysiologyand treatment of hpp, particularly the use of asfotase alfa.discussion and conclusion: despite the existence of clear clinical markers, hpp often remainsunrecognized for extended periods. treatments like asfotase alfa have significantly improvedoutcomes for severe cases in infants, children, and adults. however, questions about theoptimal duration of treatment remain. recent advancements have enhanced the understandingof hpp’s pathophysiology, particularly the role of persistently low serum alkaline phosphatase(ap) levels. increased vigilance among healthcare professionals, including dentists, orthopedicsurgeons, and rheumatologists, is crucial for timely diagnosis and management of hpp. the pastdecade has seen significant progress in understanding and treating hpp, offering new avenuesfor its management. this review encapsulates these advancements, providing a comprehensiveoverview of the evolving comprehension and approach towards this complex metabolic disorder.