Vitamin B , 2 Transport in Blood . I . Congenital Deficiency

Some characteristics of vitamin B12 bind-. IC II. Parenteral administration of high ing and transport in the serum of an infant doses of vitamin B12 was followed by rapid with congenital hereditary transcobalamin and complete clinical remission and the II (TC II) deficiency were studied using the appearance of vitamin B12 binder in the following parameters and methods: vitaa2 region which is similar to “fetal bindmm B,2 level and binding capacity; dccer.” Thus, very high concentrations of trophoretic mobility in polyacrylamide gel vitamin B12, either carrier free or bound to electrophoresis; various immunodiffusion this a2 binder, were able to correct the and absorption experiments, using a spedisturbed physiology of TC II deficiency, cific anti-TC II antiserum and the patient’s presumably by normalization of DNAserum as antigen. The results of these thymine synthesis. studies point to a deficient synthesis of U NDER PHYSIOLOGIC conditions, vitamin B,2 in human blood is bound to specific plasma proteins. The main carrier proteins are transcobalamin I and II (TC I and TC II), but several others have been described-fetal binder, leukemia binder, polycythemia binder.’ TC I and TC II are proteins with electrophoretic mobilities of a-l globulin and a-globulin, respectively, and plasma concentrations of 60 zg/liter for TC I and 25 zg/liter for TC II. The trans-cobalamins can be characterized and distinguished from each other by measuring the total vitamin B,2 binding capacity of plasma, by the distribution of this capacity in chromatographic and electrophoretic fractions, and by immunologic methods using specific antisera. Clinical studies of congenital defects or molecular anomalies may yield new data concerning their physiologic functions. We investigated an infant with congenital TC II deficiency. A few weeks after birth the child presented with severe life-threatening signs: pancytopenia due to bone marrow insufficiency, severe malabsorption due to atrophy of the intestinal mucosa, and marked hypogammaglobulinemia with absence of specific antibody production after antigenic stimulation. A rapid and complete return to normal of all these disturbances followed the parenteral administration of high doses of vitamin B,2 (e.g., neutrophils rose from 280 to 12,000 within 6 days, thrombocytes from 30 x 106 to 1060 x 106 within 11 days), and remission was maintained by weekly intramuscular injections of the vitamin. It would seem that the clinical manifestations of congenital absence of TC II can be overcome by pharmacologic doses of vitamin B,2. Family studies in our patient suggested that the deficiency was inherited as a recessive autosomal trait, similar to the families reported by Hakami et al.8 and Scott et al.9 The clinical