cobamamide and Anemia--Macrocytic

Hyperpigmentation of the hands and feet developed in a 65-year-old Korean woman who had undergone a total gastrectomy and esophagojejunostomy due to early gastric cancer 7 years previously. A diagnosis of megaloblastic anemia due to vitamin B12 deficiency was made. In the areas of pigmentation, there were abnormally large nuclei in the keratinocytes. All of these findings were reversible upon the administration of vitamin B12. Ultrastructurally, there were many intracytoplasmic desmosomes, numerous aggregated bundles of tonofilaments, and highly condensed keratohyalin granules. The pathophysiologic mechanism of vitamin B12 deficiency associated with pigmentary disturbances and change of nuclear size is discussed.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Biopsy; Cobamides; Female; Gastrectomy; Hand Dermatoses; Humans; Middle Aged; Pigmentation Disorders; Skin; Vitamin B Deficiency

We describe an inborn error of vitamin B12 metabolism in an infant who had severe developmental delay, megaloblastic anemia, and homocystinuria. There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12. Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. Cultured fibroblasts showed an absolute growth requirement for methionine, defective incorporation of radioactivity from [14C]5-methyltetrahydrofolate into protein, and normal incorporation of radioactivity from [14C]propionate, thus assigning the intracellular defect to methionine synthesis. The proportion of intracellular methylcobalamin in the fibroblasts was decreased, but that of 5'-deoxyadenosylcobalamin was normal. Methionine synthetase activity in cell extracts was normal, as was cobalamin incorporation into cultured cells. This defect differs from those described previously in being limited to methylcobalamin accumulation and defective use of 5-methyltetrahydrofolate by intact cells with normal activity of methylmalonyl CoA mutase.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Amino Acid Metabolism, Inborn Errors; Anemia, Macrocytic; Anemia, Megaloblastic; Cobamides; Fibroblasts; Homocystinuria; Humans; Hydroxocobalamin; Infant, Newborn; Male; Methionine; Propionates; Tetrahydrofolates; Vitamin B 12