Transcobalamin receptor defect: Identification of two new cases through positive newborn screening for propionic/methylmalonic aciduria and long-term outcome

Am J Med Genet A. 2018 Jun;176(6):1411-1415. doi: 10.1002/ajmg.a.38696. Epub 2018 Apr 16.

Abstract

Likely pathogenic variants in CD320 cause transcobalamin receptor defect, a recently discovered inborn errors of cobalamin metabolism. Only 12 cases have been reported to date. There are no long-term clinical and biochemical outcome reports since its first description. In this report, we present two new cases and report their long-term treatment outcome. Two asymptomatic cases were identified through a positive newborn screening for propionic/methylmalonic aciduria. Biochemical abnormalities were normalized on a short course of oral cyanocobalamin (1 mg/day). Direct sequencing of CD320 identified a known pathogenic variant (c.262_264GAG; p.Glu88del) confirming the diagnosis of transcobalamin receptor defect. To date, both patients remain asymptomatic with normal neurodevelopment more than 6 years. Our two new cases with transcobalamin receptor defect due to pathogenic variants in CD320 further expand our knowledge and provide a reassuring long-term good neurodevelopmental outcome. Identification of additional cases requires the consideration of transcobalamin receptor defect in the differential diagnosis of newborns with confirmed positive newborn screening for methylmalonic acidurias.

Keywords: CD320; cobalamin; transcobalamin receptor defect; vitamin B12 treatment.

Publication types

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

MeSH terms

  • Administration, Oral
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / drug therapy
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Antigens, CD / genetics*
  • Child
  • Humans
  • Infant, Newborn
  • Male
  • Methylmalonic Acid / blood
  • Mutation*
  • Neonatal Screening
  • Receptors, Cell Surface
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / therapeutic use

Substances

  • Antigens, CD
  • CD320 protein, human
  • Receptors, Cell Surface
  • Methylmalonic Acid
  • Vitamin B 12

Supplementary concepts

  • Methylmalonic acidemia