Transport of therapeutic cyanocobalamin in the congenital deficiency of transcobalamin II (TC II).

Cobalamin (Cbl) transport was studied in the circulation of a child deficient in transcobalamin II (TC II) after 1.0 mg of cyanocobalamin (CN-Cbl) either intramuscularly or orally. Pertinent observations include the following: (1) There was no detectable TC II in the serum as measured immunologically or by binding capacities in vivo or in vitro. (2) Transcobalamin I (TC I) was present in at least normal amounts, but, in contrast to the normal, TC I was completely saturated with Cbl. (3) The TC I of the child was qualitatively the same as that of normal persons and there was no evidence that TC I, or any other R-type binder, assumed the functions of the apparently absent TC II. (4) There was, however, an incompletely characterized circulating large molecular sized complex containing R-type binder. (5) After intake of 1.0 mg CN-Cbl orally, the usual daily therapeutic dose and route in this child, free Cbl was present in the serum. HeLa cells in culture took up free Cbl much less efficiently than Cbl bound to IC II, but the free Cbl followed the normal sequence in being bound to an intracellular binder and converted from CN-Cbl to the functioning forms adenosyl and methyl Cbl. Therefore entry to free Cbl into the child’s tissues was considered to be a therapeutic possibility.