Abstract / Summary
Background/objectives: Vitamin D-dependent rickets type 2A (VDDR2A) is caused by biallelic variants in the vitamin D receptor ( VDR ) gene. Secondary hyperparathyroidism can lead to hypophosphatemia through increased renal phosphate loss, and reduced intestinal phosphate absorption may also contribute. As a result, VDDR2A may resemble a primary hypophosphatemic disorder. Methods: We retrospectively reconstructed this child's clinical course from the available medical records, including serial laboratory results, radiographs, genetic findings, treatment changes, and follow-up. Results: The patient was referred at 3 years and 5 months with persistent lower-limb deformity, weakness, poor growth, and alopecia. He had initially been treated with calcium and vitamin D for suspected nutritional rickets. Persistent hypophosphatemia later led to a presumptive diagnosis of a primary phosphate-regulating disorder, followed by treatment with a calcium-containing phosphate preparation, additional phosphate salts, and active vitamin D. During 17 months of treatment, serum calcium was within the reference range on several occasions, whereas serum phosphate was normal only once. PTH remained markedly elevated, and the skeletal abnormalities persisted. Renal phosphate-handling indices and serum 1,25-dihydroxyvitamin D were unavailable, so the earlier diagnosis could not be confirmed biochemically. Whole-exome sequencing and parental Sanger studies identified VDR c.122G > A (p.Cys41Tyr) and c.376G > T (p.Glu126Ter) in trans; both variants were classified as likely pathogenic. No functional studies were performed. After phosphate was stopped and treatment was changed to calcium plus calcitriol, serum calcium normalized first, followed by phosphate, ALP, and PTH. Clinical and radiographic findings also improved. Conclusion: In children with rickets, serum phosphate should be interpreted together with calcium, PTH, and the overall clinical course. If PTH remains elevated or the child does not respond as expected, the diagnosis should be reconsidered. Renal phosphate handling can then be assessed when feasible, particularly when an inherited disorder is suspected.