Transcobalamins deficiencies

Dietary forms of vitamin B12 are converted to active forms in the body. Vitamin B12, mainly from liver, eggs and dairy products, is absorbed in terminal ileum. Intrinsic factor from parietal cells is required for absorption. Vitamin B12 is transported in the blood by transcobalamin II and stored in the liver. These stores are such that generally a patient does not become symptomatic until some years after the onset of vitamin B12 deficiency. 

Nexo E, Christensen A-L, Hvas A-M, et al. Quantification of holo-transcobalamin, a marker of vitamin B12 deficiency. Clin Chem 48 561-562, 2002. 

Altbougb transcobalamin II is tbe metaboUcaUy important pool of plasma vitamin B12, it accounts for only 10% to 15% of tbe total circulating vitamin. Tbe majority is bound to baptocorrin (also known as transcobalamin I). Tbe function of baptocorrin is not well understood it bas a relatively long balf-life (7 to 10 days), and does not seem to be involved in tissue uptake or intertissue transport of tbe vitamin. Altbougb genetic lack of transcobalamin 11 results in severe (and fatal) vitamin B12 deficiency, genetic lack of baptocorrin seems to bave no adverse effects. 

The daily requirement of cobalamin is about 3.0 micrograms. Absorption takes place mainly in the terminal ileum, and it is carried in plasma bound to proteins. Some 90% of recently absorbed or administered cobalamin is carried on transco-balamin II an important transport protein which is rapidly cleared from the circulation 6-9 minutes). Hereditary deficiency of transcobalamin II causes severe cobalamin deficiency. About 80% of all circulating cobalamin is bound to transcobalamin I (t) 9-12 days) which is possibly a plasma storage form (hereditary deficiency of which is of no consequence). Cobalamin in its reduced form... 

The measurement of holotranscobalamin II is potentially useftil as a specific marker of biologically available vitamin Bi2, because only cobalamin bound to Tell is specifically available for uptake by aU cells. Other methods have been described for the measurement of holotranscobalamin in serum, one using an immobilized monoclonal antibody to human transcobalamin, followed by measurement of released cobalamin by CPB, This method is currently available as a commercial kit. The other method uses magnetic beads coated with cobalamin to precipitate apotranscobalamin followed by measurement of the holotranscobalamin in the supernatant by ELISA. Though these methods are claimed to be precise and simple to perform, there remains doubt over the interpretation of the measured concentrations, and over their sensitivity and specificity in the diagnosis of vitamin B deficiency. ... 

FIGURE 53-8 The absorption and distribution of vitamin Deficiency of vitamin can result from a congenital or acquired defect in any one of the following (1) inadequate dietary supply (2) inadequate secretion of intrinsic factor (classical pernicious anemia) (3) ileal disease (4) congenital absence of transcobalamin II (Tell) or (5) rapid depletion of hepatic stores by interference with reabsorption of vitamin excreted in bile. The utility of measurements of the concentration of vitamin B 2 tn plasma to estimate supply available to tissues can be compromised by liver disease and (6) the appearance of abnormal amounts of transcobalamins I and III (Tcl and III) in plasma. Finally, the formation of methylcobalamin requires (7) normal transport into cells and an adequate supply of folic acid as CH H PteGlu. ... 

The B12 within the enterocyte complexes with transcobalamin 11 and then is released into circulation. The transcobalamin II-B12 complex delivers B12 to the tissues, which contain specific receptors for this complex. The liver takes up approximately 50% of the vitamin B12, and the remainder is transported to other tissues. The amount of the vitamin stored in the liver is large enough that 3 to 6 years pass before symptoms of a dietary deficiency occur. 

Holotranscobalamin (holoTC) HoloTC is cobalamin bound to transcobalamin and this is the available cobalamin for the cells. There is now a debate as to whether measurement of holoTC is a better marker for identifying individuals with cobalamin deficiency than total serum cobalamin. 

Chen, X., Remacha, A.F., Sarda, M.P., and Carmel, R., 2005. Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II. The American Journal of Clinical Nutrition. 81 110-114. 

Barshop BA, Wolff J, Nyhan WL, Yu A, Prodanos C, Jones G, Sweetman L, Leslie J, Holm J, Green R, Jacobsen DW, Cooper BA, Rosenblatt D (1990) Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin. Am J Med Genet 35 222-228... 

Homocystinuria and hyperhomocyst(e)inemia are biochemical denominators for deficiencies of CBS, MTHFR, cbIC-G, and transcobalamin II, the major protein carrier of cobalamin in plasma [1, 3, 6]. Patients with the latter disorder or with inborn errors of cobalamin biosynthesis resulting in combined deficiency of both adenosylcobalamin and methylcobalamin also have... 

Hereditary folate malabsorption and deficiency of transcobalamin II respond to intramuscular treatment with folinic acid and vitamin Bj2, respectively [3]. 

Tauri disease Tay-Sachs disease Testicular feminization syndrome Tetrahydrobiopterin deficiency Thiopurine methyltransferase deficiency Thymidine phosphorylase deficiency Transcobalamin II deficiency Tricho-hepato-enteric syndrome Trimethylaminuria Tripeptidyl peptidase I deficiency Tryptophan-2,3-dioxygenase deficiency Tryptophanuria... 

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