HYPOPHOSPHATEMIC RICKETS AND ITS GENETIC AND CLINICAL COMPLEXITY: AN INTEGRATIVE LITERATURE REVIEW

Abstract

Hypophosphatemic rickets, a rare genetic disease characterized by hypophosphatemia resulting from excessive renal phosphate loss, leads to defects in bone mineralization. It is a group of conditions, with particular emphasis on the X-linked form associated with mutations in the PHEX gene. The pathophysiology mainly involves the action of FGF23, which reduces renal phosphate reabsorption and vitamin D activation. Clinically, it manifests in childhood with bone deformities, growth retardation, bone pain, and dental abnormalities, and may progress to osteomalacia in adulthood. This integrative review analyzed studies published between 1997 and 2025, addressing genetic, pathophysiological, and therapeutic aspects of the disease. The results highlight the diversity of genetic mutations, especially in the PHEX gene, and different inheritance patterns (X-linked, autosomal dominant and recessive, as well as forms not mediated by FGF23). Traditional treatment is based on phosphate and vitamin D replacement, while recent therapies, such as burosumab, act directly on the inhibition of FGF23, representing a significant advance. It is concluded that early diagnosis, combined with genetic evaluation and continuous clinical follow-up, is essential to improve the prognosis and quality of life of patients, and further studies are needed to deepen our understanding of the disease.