Identification of two novel transcobalamin 2 variants associated with developmental delay and megaloblastic anaemia in infancy

To the Editor,
Cobalamin (vitamin B12) is a water soluble vitamin that is crucial for DNA synthesis and cell metabolism. Transcobalamin (TC, formerly transcobalamin II) is a cobalamin binding protein required for cellular uptake of the vitamin via membrane receptor mediated endocytosis, since cobalamin is unable to cross the cellular plasma membrane in physiological quantities. Holotranscobalamin (also called ‘active B12’) is the complex of TC bound to cobalamin and represents the physiologically active fraction of total vitamin B12. Once inside the cell, holotranscobalamin is degraded and cobalamin is processed into its active co-enzyme forms, methylcobalamin and 5-deoxyadenosylcobalamin.

Congenital TC deficiency is a rare, autosomal recessive disorder caused by abnormalities in the TCN2 gene, which is located on chromosome 22q12. The disorder typically manifests in the first year of life with neurological, haematological and immunological complications...