Genetic patterns of transcobalamin II and the relationships with congenital defects

Mol Cell Biochem. 1983;56(1):5-31. doi: 10.1007/BF00228765.


The vitamin B12-binding protein, transcobalamin II, is a trace component of plasma with a rapid turnover. This protein is essential for absorption, transport, cellular uptake and for recycling of vitamin B12 (cobalamin). Congenital transcobalamin II deficiency, an inborn error of metabolism is inherited as a recessive trait. The homozygous form of the deficiency is accompanied by severe clinical, hematological and immunological disturbances in the first months of life. Analytical, genetic, biochemical and clinical aspects of transcobalamin II in man and in vertebrates have been reviewed here. A genetic polymorphism for the protein has been found in man, rabbits and mice. Family studies revealed that the genetic patterns in man are determined by four polymorphic and several rare alleles. This genetic variability has been applied in paternity testing and in population studies. Transcobalamin II typing in families of patients with the inherited functional deficiency has led to identification of various deficient alleles in heterozygous carriers of the defects. Applying transcobalamin II typing after bone marrow transplantation demonstrated that this protein originates partly in the bone marrow. Subsequent investigations in cell culture have shown that human skin fibroblasts and cultured bone marrow synthesize and secret isotypes of a transport protein corresponding to the genetic isotypes observed in plasma. Comparison of transcobalamin II types in umbilical cord serum with the maternal types, has proven that the transcobalamin II activity in the cord serum is derived from the fetus. This finding will be of crucial importance in the early diagnosis of the deficiency syndrome.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Child
  • Congenital Abnormalities / etiology
  • Congenital Abnormalities / genetics*
  • Female
  • Genes, Dominant
  • Genetic Carrier Screening
  • Genetic Linkage
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Polymorphism, Genetic
  • Transcobalamins / deficiency
  • Transcobalamins / genetics*
  • Transcobalamins / isolation & purification
  • Vitamin B 12 / metabolism


  • Transcobalamins
  • Vitamin B 12