Non-nutritional rickets (NNR) or refractory rickets encompasses a heterogeneous group of inherited and acquired disorders characterized by defective bone mineralization independent of dietary vitamin D or calcium deficiency. This narrative review synthesizes current evidence on the pathophysiology, clinical presentation, biochemical and radiological diagnosis, and management of the principal NNR subtypes: X-linked hypophosphatemic rickets, autosomal dominant/recessive hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria, tumor-induced osteomalacia, vitamin D-dependent rickets types 1 and 2, and hypophosphatasia. The transformative role of burosumab (anti-fibroblast growth factor 23 monoclonal antibody) and asfotase alfa (enzyme replacement therapy) is highlighted alongside emerging molecular therapies. Diagnostic algorithm and comprehensive comparison tables are provided to guide clinicians in timely identification and individualized treatment, aiming to improve long-term musculoskeletal and quality-of-life outcomes in affected children.
Bala et al. (Wed,) studied this question.