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

N Engl J Med. 2019 Mar 21;380(12):1150-1157. doi: 10.1056/NEJMoa1807841.

Abstract

A 58-year-old woman with debilitating ankylosing spondylitis who was born to consanguineous parents was found to have an apparent severe vitamin D deficiency that did not respond to supplementation. Liquid chromatography-tandem mass spectrometry showed the absence of circulating vitamin D-binding protein, and chromosomal microarray confirmed a homozygous deletion of the group-specific component (GC) gene that encodes the protein. Congenital absence of vitamin D-binding protein resulted in normocalcemia and a relatively mild disruption of bone metabolism, in this case complicated by severe autoimmune disease. (Funded by the National Institutes of Health and the University of Washington.).

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoimmune Diseases / complications*
  • Calcium / blood
  • Chromatography, Liquid
  • Female
  • Fractures, Spontaneous / etiology
  • Gene Deletion*
  • Gene Expression
  • Homozygote
  • Humans
  • Hydroxycholecalciferols / blood*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Siblings
  • Spondylitis, Ankylosing / complications
  • Spondylitis, Ankylosing / genetics*
  • Tandem Mass Spectrometry
  • Vitamin D / metabolism
  • Vitamin D Deficiency / genetics*
  • Vitamin D-Binding Protein / deficiency
  • Vitamin D-Binding Protein / genetics*

Substances

  • Hydroxycholecalciferols
  • Vitamin D-Binding Protein
  • Vitamin D
  • Calcium