Transcobalamin (TC) is the plasma transporter that delivers vitamin B(12) to cells. We have already reported that HT-29 and Caco-2 cells secrete different TC variants. HT-29 secretes 2 TC isoproteins (codon 259-Pro/Arg [259-P/R]), exhibiting unequal concentrations (TC 259-P > TC 259-R), and Caco-2 cells only secrete the phenotype 259-R. We investigated the relation between phenotypic and genetic TC polymorphism in HT-29 cells transfected with Caco-2 TC complementary DNA and in 159 healthy Caucasians. We found that codon 259-R is buried and, thus, the genetic polymorphism provides no explanation why the TCs from HT-29 and Caco-2 cells have different isoelectric points in nondenaturing isoelectric focusing (IEF). The newly translated TC in HT-29 cells from the Caco-2 complementary DNA recombinant plasmid had the same isoelectric point as the TC constitutively expressed in HT-29 cells, suggesting that TC phenotypic variability involves a specific cell folding of the protein. The codon 259 polymorphism was found to have a biallelic distribution: homozygotes P = 34.6%, heterozygotes R/P = 47.8%, and homozygotes R = 17.6%. In heterozygous samples, the IEF showed that the TC 259-P/TC 259-R ratio = 1.6. The blood apo-TC concentration of 259-P homozygous Caucasians was significantly higher than that of homozygous 259-R (P <.0001) and heterozygous (P <.0006) Caucasians. The heterozygotes 259-R/P had homocysteine concentration significantly higher than the homozygotes 259-R and 259-P (P =.02 and P =.01, respectively). In conclusion, TC codon-259 polymorphism affects TC plasma concentration and may interfere in vitamin B(12) cellular availability and homocysteine metabolism.

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Hyperhomocysteinemia has been associated with several pregnancy complications. We have investigated the variation of plasma total homocysteine (tHcys) during the 2 last trimesters of normal pregnancy and related it to blood vitamin B12 and folate and to the excretion of the degraded intrinsic factor receptor (IFCR) in urine, in a follow-up study of 15 cases. A significant rise in tHcys was observed between the beginning of the second trimester and the third trimester with respective values (median) 6.1, 5.8 and 6.7 micromol/l (p = 0.038). The tHcys/albumin ratio also increased significantly, while no correlation was found between albumin and folate blood concentration. In contrast, a significant decrease in vitamin B12 was observed (279, 225 and 199 pmol/l, between the 4th and 6th, and the 6th and 9th month, respectively (p = 0.017-0.002)). A significant negative correlation was found between tHcys between the 4th and 9th month of pregnancy and the ratio of vitamin B12 between the 4th and 9th month of pregnancy (r = 0.55, p = 0.037). The urine excretion of IFCR was increased and was not related to vitamin B12 and tHcys. In conclusion, we have observed a rise in tHcys between the beginning of the second trimester and the third trimester of pregnancy which was related to the decreased blood level of vitamin B12. Subclinical deficiency of vitamin B12 should be further investigated in pregnant women who remain on inadequate diet.

Background: Customary blood protein markers for malnutrition are of limited value in the diagnosis of protein-energy malnutrition or anorexia nervosa in children and in the follow-up to refeeding in such children. Objectives: For these diseases, we compared the diagnostic value of sex hormone binding globulin (SHBG) with that of albumin, transferrin, transthyretin, and retinal binding protein and determined the relations between concentrations of insulin, insulinlike growth factor I, and SHBG. Design: SHBG was assayed in children with protein-energy malnutrition (29 children with kwashiorkor and 28 with marasmus), in 29 anorectic girls (before and after refeeding), and in age-and sex-matched control subjects. Results: Mean (± SE) serum SHBG concentrations were higher in the children with kwashiorkor (0.18 ± 0.07 mol/L) than in the children with marasmus (0.11 ± 0.05 mol/L, P < 0.0001) or the control subjects (0.11 ± 0.03 mol/L, P < 0.0005). In the children with anorexia nervosa before weight gain, serum SHBG concentrations were significantly higher (0.10 ± 0.04 mol/L) than in the age-matched control subjects (0.06 ± 0.03 mol/L, P < 0.001) and decreased significantly after 30 d of refeeding (0.04 ± 0.01 mol/L, P < 0.0001). This decrease was negatively correlated with insulin-like growth factor I but not with insulin. Mean serum SHBG concentrations were influenced neither by inflammation, as indicated when C-reactive protein was used as a marker (0.27 ± 0.27, 0.34 ± 0.42, and < 0.04 mol/L in the children with marasmus, kwashiorkor, and anorexia nervosa, respectively), nor by glomerular filtration, as indicated when cystatin-C was used as a marker (68.46 ± 23.08, 66.90 ± 43.08, and 49.23 ± 7.69 mol/L, respectively). Conclusions:The high SHBG concentration observed in anorexia nervosa and kwashiorkor seems to be of multifactorial origin. For these 2 diseases, SHBG is a reliable marker of nutritional status, is unrelated to either C-reactive protein or cystatin-C, and may be helpful in distinguishing kwashiorkor from marasmus and as a follow-up marker after refeeding. Am J Clin Nutr 2002;76:239-44. KEY WORDSSex hormone binding globulin, anorexia nervosa, kwashiorkor, marasmus, malnutrition, inflammation, renal failure, insulin-like growth factor I, insulin INTRODUCTIONThe term protein-energy malnutrition (PEM) is widely used to describe a group of diseases (2 extreme forms, kwashiorkor and marasmus, and many mixed forms) that often affect young children in most developing countries. Inflammation and changes in hormonal patterns are usually associated with kwashiorkor and marasmus. For a long time, kwashiorkor and marasmus have been considered to be the clinical translation of either inadequate protein intake or deficient energy intake (1). However, it has been observed that kwashiorkor and marasmus may coexist in the same infantile population having the same diet (2). More recently, kwashiorkor has been considered a metabolic misadaptation of the organism to malnutrition, explaining the development of edema. ...