A patient with the inability to maintain in vivo levels of bound cobalamin (Cbl) and manifestations of tissue deficiency of Cbl

Abstract

A 39-year-old woman presented with mild anemia, glossitis, an increased MCV, a low serum cobalamin (Cbl) (vitamin B12), mild tissue deficiency of Cbl, but with neither malabsorption of Cbl, impaired intake, nor deficiency of or inactivity of transcobalamin II (TC II). Because of a persistently low holo-TC II (TC II carrying Cbl as the circulating complex of TC II-Cbl), much of the evaluation was focused on the patient's TC II. Her TC II promoted the uptake of Cbl, reacted with anti-TC II, and bound Cbl in vitro. A test dose of 200 micrograms of cyanocobalamin (CN-Cbl) i.m. increased her holo TC II to levels higher than those in healthy persons, but with a much more abrupt fall to a subnormal level. Two milligrams of CN-Cbl i.m. followed by 100 micrograms i.m. monthly failed to maintain normal amounts of circulating TC II-Cbl or to overcome the tissue deficiency of Cbl. One milligram i.m. weekly or daily p.o. corrected both. The low holo TC II was considered to be responsible for the clinical expression and may have been primary to the reduced amounts of total and holo R binder of Cbl in the circulation. This study of a newly recognized defect points out the need for circulating holo TC II, a rational use of pharmacologic amounts of Cbl, and a possible interrelationship between TC II and the R binder of Cbl.