Endocrine Abstracts

JOINT2366

Background: Vitamin D-dependent rickets type 2A (VDDR2A) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene, leading to resistance to 1, 25-dihydroxyvitamin D. It results in hypocalcemia, secondary hyperparathyroidism, and severe rickets. Alopecia is a hallmark feature, particularly in cases with mutations in the DNA-binding domain of the VDR gene. We report a case of VDDR2A in a 1-year-old girl presenting with jerking movements and alopecia.

Case Report: A previously healthy 1-year-old girl presented with brief jerking movements involving the trunk and upper extremities, initially occurring once daily and increasing in frequency. There was no history of seizures, consanguinity, or family history of epilepsy. She was born full-term with normal birth weight and had no perinatal complications. Growth parameters were within normal limits, but gross motor development was delayed. Physical examination revealed diffuse alopecia, frontal bossing, and absent teeth. Chvostek’s sign was positive, suggesting hypocalcemia. Laboratory investigations showed hypocalcemia, low-normal phosphorus, elevated alkaline phosphatase (1, 677 U/l), and markedly elevated parathyroid hormone (565 ng/l). Her 1, 25-dihydroxyvitamin D level was strikingly high (>1, 500 pmol/l). Radiographs revealed classic rickets features. Whole-exome sequencing identified a homozygous c. 238C>T (p. Arg80*) mutation in the VDR gene, confirming VDDR2A. She was initially treated with intravenous calcium gluconate for symptomatic hypocalcemia, followed by high-dose oral calcium (up to 285 mg/kg/day) and calcitriol (0. 6 mg/kg/day). Over seven months, her biochemical markers and radiological features significantly improved. By 1 year and 11 months, healing was evident, and treatment was gradually reduced. However, alopecia persisted. Her motor development improved, and her height velocity increased from 2 cm over six months to 6. 2 cm in the following six months.

Discussion: This case highlights the importance of considering VDDR2A in infants with early-onset rickets, hypocalcemia, and alopecia. The key diagnostic clue is high 1, 25-dihydroxyvitamin D despite hypocalcemia and secondary hyperparathyroidism. Mutations in the DNA-binding domain of the VDR gene cause complete receptor dysfunction, resulting in severe disease and alopecia.

Conclusion: Early recognition and genetic confirmation of VDDR2A are crucial for timely intervention. High-dose calcium and calcitriol therapy improve biochemical markers and bone health, but alopecia remains irreversible. Long-term follow-up is necessary to adjust treatment as calcium homeostasis changes with age.