Transcobalamin receptor defect: Identification of two new cases through positive newborn screening for...

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.