Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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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.
Mol Cell Biochem 1983
PMID:Genetic patterns of transcobalamin II and the relationships with congenital defects. 635 16

Transcobalamin II deficiency (# MIM 275350) is a rare, recessively inherited disorder of cobalamin transport that leads to intracellular cobalamin depletion with secondary impairment of methionine synthetase and methyl-malonyl CoA mutase activities. Affected individuals may suffer from long-term neurological sequelae if therapy with intramuscular hydroxocobalamin is not initiated promptly. We report two sisters with complete absence of transcobalamin due to homozygosity for a novel mutation (c.insC110) in the TCN2 gene that leads to a premature stop codon and non-functional protein. The older sister, now 4.5 years old, presented at 6 weeks of age with pancytopenia, protein losing enteropathy and a rapidly declining clinical course. Prompt therapy with 1mg hydroxocobalamin/day led to full recovery within days. Her now 1.5 year old sister was diagnosed shortly after birth and was started on hydroxocobalamin prior to onset of clinical symptoms. Interestingly, urinary methylmalonic acid excretion was increased significantly during the first days of life suggesting that functional cobalamin deficiency is present also during fetal life, although not giving rise to clinical symptoms until well after birth.
Mol Genet Metab 2009 Nov
PMID:Transcobalamin II deficiency at birth. 1958 Nov 17