Biallelic loss-of-function mutations in BPNT1 cause vitamin B12-dependent megaloblastic anemia

Abstract

We identified biallelic loss-of-function BPNT1 mutations in three patients with recurrent vitamin B12-dependent megaloblastic anemia. Mechanistically, BPNT1 deficiency caused accumulation of 3'-phosphoadenosine 5'-phosphate (PAP), impaired ribosome biogenesis, and reduced ileal expression of the cubam receptor complex in Bpnt1-null mice.