Endocrine Abstracts

JOINT2201

Background: Vitamin D-dependent rickets type 2A (VDDR2A) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor gene (VDR), which is marked by end-organ resistance to 1,25-dihydroxy vitamin D (1,25(OH)₂D). The phenotype varies depending on the VDR’s domain affected, and alopecia is typically included.

Objective: To investigate the genotype and its correlation with alopecia in a VDDR2A case.

Methods: A consanguineous family of Chinese Han origin with one proband of VDDR2A was recruited. The patient was evaluated clinically, biochemically and radiographically. Gene sequencing was performed to all family members.

Results: The 3-year-old proband showed early-onset alopecia, rickets, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, elevated alkaline phosphatase and low level of 25-hydroxy vitamin D (25(OH)D). He had compound heterozygous variants of VDR. c.376G>T(p.E126*) was a novel mutation, mainly affecting Ligand-binding domain. The other variant, c.122G>A(p.C41Y), which was restricted to DNA-binding domain, had been identified to cause alopecia in homozygotes. The proband presented mild alopecia compared with homozygotes of c.122G>A mutation.

Conclusion: We identified a novel VDR mutation in a compound heterozygote. Though alopecia is the typical clinical feature of VDDR2A, this phenotype could be variable depending on the synergy of alleles.

Keywords: Rickets, VDDR2A, VDR, Alopecia