Hypophosphatemic rickets in children: current knowledge and a proposal for a diagnostic algorithm.

Abstract

Hypophosphatemic rickets (HR) are a heterogeneous group of disorders characterized by chronic hypophosphatemia, impaired mineralizationof bone and growth plates, and lifelong skeletal complications. This review summarizes the current knowledge on genetic and acquiredforms of HR in children, including X-linked hypophosphatemia (XLH), autosomal dominant and recessive forms, tumor-induced osteomalacia,and other rare syndromes. Clinical presentation typically includes limb deformities, growth retardation, bone pain, and dentalabnormalities, while complications in adulthood may involve osteomalacia, enthesopathies, and cardiovascular issues. Diagnosis relies ondetailed medical history, physical examination, biochemical evaluation, radiological imaging, and genetic testing. We propose a diagnosticalgorithm for children to facilitate early recognition, appropriate differentiation of FGF23-dependent and -independent forms, and timely intervention. The review also outlines conventional and targeted therapies, highlighting the role of burosumab in FGF23-mediated formsand the need for individualized management in rare or FGF23-independent HR. Early diagnosis and a multidisciplinary approach arecrucial to optimize outcomes and improve quality of life.