A case of vitamin D-dependent rickets type 2A presenting with hypophosphatemia without hypocalcemia

Vitamin D is essential for calcium and phosphate homeostasis and skeletal development. Variants in the vitamin D receptor gene (VDR) cause vitamin D-dependent rickets type 2A (VDDR2A), characterized by end-organ resistance to 1,25-dihydroxyvitamin D (1,25(OH)₂D). We describe a child of nonconsanguineous Middle Eastern parents who presented at age 9 months with poor linear growth and inadequate weight gain. Initial evaluation showed normocalcemia, hypophosphatemia, hyperparathyroidism, markedly elevated alkaline phosphatase, and radiographic rickets, leading to an initial diagnosis of hypophosphatemic rickets. Despite treatment with low-dose calcitriol, cholecalciferol, calcium, phosphate, and bicarbonate, biochemical abnormalities persisted. Further evaluation revealed markedly elevated 1,25(OH)₂D, and whole-exome sequencing identified a homozygous pathogenic VDR c.1027C>T (p.R343C) variant, confirming VDDR2A. High-dose calcitriol therapy resulted in progressive biochemical improvement and catch-up growth. This case highlights that VDDR2A may initially present with hypophosphatemia without hypocalcemia, leading to misclassification as hypophosphatemic rickets. Early recognition of elevated 1,25(OH)₂D and timely genetic testing are essential for accurate diagnosis and management.