Vitamin D-dependent rickets: challenges in diagnosis and management

Abstract

Vitamin D-dependent rickets type II (VDDR-II) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor gene, leading to end-organ resistance to 1,25-dihydroxyvitamin D and poor response to conventional therapy. We report an adolescent female with genetically confirmed VDDR-II who presented with severe skeletal deformities, recurrent fractures, profound hypocalcaemia, secondary hyperparathyroidism, growth failure, and partial alopecia. Clinical, biochemical, radiological, and genetic evaluations confirmed the diagnosis. Despite intensive treatment with high-dose oral calcitriol and calcium supplementation, the patient required frequent intravenous calcium infusions to achieve partial biochemical stabilization, reflecting the resistant nature of the disease. Long-term follow-up demonstrated persistent growth impairment and fluctuating biochemical parameters closely related to treatment adherence. Notably, her sibling carrying the same vitamin D receptor mutation exhibited a significantly milder clinical phenotype, highlighting marked intrafamilial variability. This case illustrates the diagnostic and therapeutic challenges associated with VDDR-II and emphasizes the importance of early recognition, strict adherence to therapy, and multidisciplinary management to reduce complications and optimize outcomes.