Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric aciduria Type 2, is caused by a microdeletion in the riboflavin transporter gene GPR172B

Hum Mutat. 2011 Jan;32(1):E1976-84. doi: 10.1002/humu.21399.


Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by riboflavin supplementation. The mother was then found to be persistently riboflavin deficient, suggesting that a possible genetic defect in riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this riboflavin transporter causes mild riboflavin deficiency, and when coupled with nutritional riboflavin deficiency in pregnancy, resulted in the transient riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in riboflavin transport in humans.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Copy Number Variations
  • Exons
  • Female
  • Gene Deletion
  • Genotype
  • HEK293 Cells
  • Humans
  • Infant, Newborn
  • Male
  • Membrane Transport Proteins / genetics*
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / etiology*
  • Pedigree
  • Receptors, G-Protein-Coupled / genetics*
  • Riboflavin Deficiency / complications*
  • Riboflavin Deficiency / genetics*


  • Membrane Transport Proteins
  • Receptors, G-Protein-Coupled
  • SLC52A1 protein, human