Vitamin D–Binding Protein Deficiency and Homozygous Deletion of the GC Gene

This brief report describes a 58 year old woman with severe ankylosing spondylitis and consanguineous parentage who exhibited undetectable vitamin D levels despite supplementation. Mass spectrometry revealed a complete absence of vitamin D binding protein (VDBP), and chromosomal analysis confirmed a homozygous deletion of the GC gene encoding VDBP. Despite lifelong VDBP deficiency, the patient maintained normocalcemia and showed only mild bone metabolism disruption (osteopenia and fragility fractures), contrasting with her undetectable 25 hydroxyvitamin D levels. The case challenges conventional metrics of vitamin D status and supports the "free hormone hypothesis," suggesting that bioavailable vitamin D (unbound to VDBP) may suffice for calcium homeostasis. The study highlights the complex interplay between VDBP, vitamin D metabolism, and autoimmune disease.

This brief report describes a 58 year old woman with severe ankylosing spondylitis and consanguineous parentage who exhibited undetectable vitamin D levels despite supplementation. Mass spectrometry revealed a complete absence of vitamin D binding protein (VDBP), and chromosomal analysis confirmed a homozygous deletion of the GC gene encoding VDBP. Despite lifelong VDBP deficiency, the patient maintained normocalcemia and showed only mild bone metabolism disruption (osteopenia and fragility fractures), contrasting with her undetectable 25 hydroxyvitamin D levels. The case challenges conventional metrics of vitamin D status and supports the "free hormone hypothesis," suggesting that bioavailable vitamin D (unbound to VDBP) may suffice for calcium homeostasis. The study highlights the complex interplay between VDBP, vitamin D metabolism, and autoimmune disease.