Skip to main content
SpringerLink
Log in

Cobalamin status in children

  • Homocysteine and B-Vitamin Metabolism
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Cobalamin and the metabolic markers methylmalonic acid and total homocysteine undergo marked changes during childhood. In breastfed infants a metabolic profile indicative of cobalamin deficiency is common. Symptoms of cobalamin deficiency in children differ with age, presenting a continuum from subtle developmental delay to life-threatening clinical conditions. The symptoms may be difficult to detect, particularly in infants, and there tends to be a diagnostic delay of several months in this age group. Several reports show that even moderate deficiency in children may be harmful, and long-term consequences of neurological deterioration may persist after cobalamin deficiency has been treated. Given the crucial role of cobalamin for normal growth and development, possible widespread infantile deficiency needs attention. Cobalamin deficiency should be considered a differential diagnosis in children with subtle symptoms, and strategies to prevent cobalamin deficiency in mothers and children should be addressed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

BMI:

body mass index

methylmalonyl CoA mutase:

methylmalonyl coenzyme A mutase

MMA:

methylmalonic acid

MRI:

magnetic resonance imaging

PPI:

proton-pump inhibitors

RDA:

recommended dietary allowances

tHcy:

total homocysteine

WHO:

World Health Organization

References

  • Allen LH (1994) Vitamin B12 metabolism and status during pregnancy, lactation and infancy. Adv Exp Med Biol 352:173–186

    CAS  PubMed  Google Scholar 

  • Allen LH (2002) Impact of vitamin B-12 deficiency during lactation on maternal and infant health. Adv Exp Med Biol 503:57–67

    CAS  PubMed  Google Scholar 

  • Allen LH (2004) Folate and vitamin B12 status in the Americas. Nutr Rev 62:S29–S33, discussion S34

    PubMed  Google Scholar 

  • Allen LH (2009) How common is vitamin B-12 deficiency? Am J Clin Nutr 89:693S–696S

    CAS  PubMed  Google Scholar 

  • Allen RH, Stabler SP, Savage DG, Lindenbaum J (1993) Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J 7:1344–1353

    CAS  PubMed  Google Scholar 

  • Audelin MC, Genest J Jr (2001) Homocysteine and cardiovascular disease in diabetes mellitus. Atherosclerosis 159:497–511

    CAS  PubMed  Google Scholar 

  • Avci Z, Turul T, Aysun S, Unal I (2003) Involuntary movements and magnetic resonance imaging findings in infantile cobalamine (vitamin B12) deficiency. Pediatrics 112:684–686

    PubMed  Google Scholar 

  • Baker SJ, Ignatius M, Johnson S, Vaish SK (1963) Hyperpigmentation of skin. A sign of vitamin-B12 deficiency. Br Med J 1:1713–1715

    CAS  PubMed  Google Scholar 

  • Baker H, Thind IS, Frank O, DeAngelis B, Caterini H, Louria DB (1977) Vitamin levels in low-birth-weight newborn infants and their mothers. Am J Obstet Gynecol 129:521–524

    CAS  PubMed  Google Scholar 

  • Benbir G, Uysal S, Saltik S et al (2007) Seizures during treatment of Vitamin B12 deficiency. Seizure 16:69–73

    CAS  PubMed  Google Scholar 

  • Bennett M (2001) Vitamin B12 deficiency, infertility and recurrent fetal loss. J Reprod Med 46:209–212

    CAS  PubMed  Google Scholar 

  • Bjorke Monsen AL, Ueland PM (2003) Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence. Am J Clin Nutr 78:7–21

    PubMed  Google Scholar 

  • Bjorke Monsen AL, Ueland PM, Vollset SE et al (2001) Determinants of cobalamin status in newborns. Pediatrics 108:624–630

    CAS  PubMed  Google Scholar 

  • Bjorke-Monsen AL, Torsvik I, Saetran H, Markestad T, Ueland PM (2008) Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation. Pediatrics 122:83–91

    PubMed  Google Scholar 

  • Black MM (2008) Effects of vitamin B12 and folate deficiency on brain development in children. Food Nutr Bull 29:S126–S131

    PubMed  Google Scholar 

  • Black AK, Allen LH, Pelto GH, de Mata MP, Chavez A (1994) Iron, vitamin B-12 and folate status in Mexico: associated factors in men and women and during pregnancy and lactation. J Nutr 124:1179–1188

    CAS  PubMed  Google Scholar 

  • Bondevik GT, Schneede J, Refsum H, Lie RT, Ulstein M, Kvale G (2001) Homocysteine and methylmalonic acid levels in pregnant Nepali women. Should cobalamin supplementation be considered? Eur J Clin Nutr 55:856–864

    CAS  PubMed  Google Scholar 

  • Bor MV, von Castel-Roberts KM, Kauwell GP et al (2010) Daily intake of 4 to 7 microg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population. Am J Clin Nutr 91:571–577

    CAS  PubMed  Google Scholar 

  • Butte NF, Lopez-Alarcon MG, Garza C (2002) Nutrient adequacy of exclusive breast feeeding for the term infant during the first six months of life. World Health Institution, Geneva

    Google Scholar 

  • Carmel R (2000) Current concepts in cobalamin deficiency. Annu Rev Med 51:357–375

    CAS  PubMed  Google Scholar 

  • Carmel R, Green R, Rosenblatt DS, Watkins D (2003) Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program 62–81

  • Casella EB, Valente M, de Navarro JM, Kok F (2005) Vitamin B12 deficiency in infancy as a cause of developmental regression. Brain Dev 27:592–594

    PubMed  Google Scholar 

  • Castle WB, Hale TH (1998) Vitamin B12. In: Combs GF (ed) The vitamins: fundamental aspects in nutrition and health, Academic, San Diego, pp 403–420

  • Cetinkaya F, Yildirmak Y, Kutluk G, Erdem E (2007) Nutritional vitamin B12 deficiency in hospitalized young children. Pediatr Hematol Oncol 24:15–21

    CAS  PubMed  Google Scholar 

  • Chen Z, Chakraborty S, Banerjee R (1995) Demonstration that mammalian methionine synthases are predominantly cobalamin-loaded. J Biol Chem 270:19246–19249

    CAS  PubMed  Google Scholar 

  • Collier S, Fulhan J, Duggan C (2004) Nutrition for the pediatric office: update on vitamins, infant feeding and food allergies. Curr Opin Pediatr 16:314–320

    PubMed  Google Scholar 

  • Coulthard H, Harris G, Emmett P (2009) Delayed introduction of lumpy foods to children during the complementary feeding period affects child’s food acceptance and feeding at 7 years of age. Matern Child Nutr 5:75–85

    PubMed  Google Scholar 

  • Craft IL, Matthews DM, Linnell JC (1971) Cobalamins in human pregnancy and lactation. J Clin Pathol 24:449–455

    CAS  PubMed  Google Scholar 

  • Dagnelie PC, Van Staveren WA, Hautvast JG (1985) Health and nutritional status of ‘alternatively’ fed infants and young children, facts and uncertainties. II. Specific nutritional deficiencies; discussion. Tijdschr Kindergeneeskd 53:208–216

    CAS  PubMed  Google Scholar 

  • De Laet C, Wautrecht JC, Brasseur D et al (1999) Plasma homocysteine concentration in a Belgian school-age population. Am J Clin Nutr 69:968–972

    PubMed  Google Scholar 

  • Delvin EE, Rozen R, Merouani A, Genest J Jr, Lambert M (2000) Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children. Am J Clin Nutr 72:1469–1473

    CAS  PubMed  Google Scholar 

  • Dror DK, Allen LH (2008) Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev 66:250–255

    PubMed  Google Scholar 

  • Emery ES, Homans AC, Colletti RB (1997) Vitamin B12 deficiency: a cause of abnormal movements in infants. Pediatrics 99:255–256

    CAS  PubMed  Google Scholar 

  • Fedosov SN (2010) Metabolic signs of vitamin B(12) deficiency in humans: computational model and its implications for diagnostics. Metabolism doi:10.1016/j.physletb.2003.10.071

    PubMed  Google Scholar 

  • Fewtrell MS, Morgan JB, Duggan C et al (2007) Optimal duration of exclusive breastfeeding: what is the evidence to support current recommendations? Am J Clin Nutr 85:635S–638S

    CAS  PubMed  Google Scholar 

  • Finnell RH, Shaw GM, Lammer EJ, Rosenquist TH (2008) Gene-nutrient interactions: importance of folic acid and vitamin B12 during early embryogenesis. Food Nutr Bull 29:S86–S98, discussion S99–100

    PubMed  Google Scholar 

  • Fokkema MR, Weijer JM, DijckBrouwer DAJ, vanDoormaal JJ, Muskiet FAJ (2001) Influence of vitamin-optimized plasma homocysteine cutoff values on the prevalence of hyperhomocysteinemia in healthy adults. Clin Chem 47:1001–1007

    CAS  PubMed  Google Scholar 

  • Ford C, Rendle M, Tracy M, Richardson V, Ford H (1996) Vitamin B12 levels in human milk during the first nine months of lactation. Int J Vitam Nutr Res 66:329–331

    CAS  PubMed  Google Scholar 

  • Fowler B, Leonard JV, Baumgartner MR (2008) Causes of and diagnostic approach to methylmalonic acidurias. J Inherit Metab Dis 31:350–360

    CAS  PubMed  Google Scholar 

  • Frery N, Huel G, Leroy M et al (1992) Vitamin B12 among parturients and their newborns and its relationship with birthweight. Eur J Obstet Gynecol Reprod Biol 45:155–163

    CAS  PubMed  Google Scholar 

  • Garewal G, Narang A, Das KC (1988) Infantile tremor syndrome: a vitamin B12 deficiency syndrome in infants. J Trop Pediatr 34:174–178

    CAS  PubMed  Google Scholar 

  • George L, Mills JL, Johansson AL et al (2002) Plasma folate levels and risk of spontaneous abortion. JAMA 288:1867–1873

    CAS  PubMed  Google Scholar 

  • Gilliam JN, Cox AJ (1973) Epidermal changes in vitamin B 12 deficiency. Arch Dermatol 107:231–236

    CAS  PubMed  Google Scholar 

  • Graham I, Meleady R (1996) Heart attacks and homocysteine—time for a randomised controlled trial of plasma homocysteine reduction. Br Med J 313:1419–1420

    CAS  Google Scholar 

  • Graham SM, Arvela OM, Wise GA (1992) Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 121:710–714

    CAS  PubMed  Google Scholar 

  • Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA (1997) The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements. Mov Disord 12:39–46

    CAS  PubMed  Google Scholar 

  • Guerra-Shinohara EM, Paiva AA, Rondo PH, Yamasaki K, Terzi CA, D’Almeida V (2002) Relationship between total homocysteine and folate levels in pregnant women and their newborn babies according to maternal serum levels of vitamin B12. BJOG 109:784–791

    CAS  PubMed  Google Scholar 

  • Hall CA (1990) Function of vitamin B12 in the central nervous system as revealed by congenital defects. Am J Hematol 34:121–127

    CAS  PubMed  Google Scholar 

  • Heath ML, Sidbury R (2006) Cutaneous manifestations of nutritional deficiency. Curr Opin Pediatr 18:417–422

    PubMed  Google Scholar 

  • Honzik T, Adamovicova M, Smolka V, Magner M, Hruba E, Zeman J (2010) Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B(12) deficiency—What have we learned? Eur J Paediatr Neurol: (Epub ahead of print)

  • Indrio F, Riezzo G, Raimondi F, Cavallo L, Francavilla R (2009) Regurgitation in healthy and non healthy infants. Ital J Pediatr 35:39

    PubMed  Google Scholar 

  • Institute of Medicine (1990) Nutrition during pregnancy. National Academy Press, Washington

    Google Scholar 

  • Institute of Medicine (1998) Dietary reference intakes: thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academy Press, Washington

    Google Scholar 

  • Jadhav M, Webb JKG, Vaishnava S, Baker SJ (1962) Vitamin B12 deficiency in Indian infants. Lancet 2:903–907

    CAS  PubMed  Google Scholar 

  • Kempf K, Rathmann W, Herder C (2008) Impaired glucose regulation and type 2 diabetes in children and adolescents. Diabetes Metab Res Rev 24:427–437

    CAS  PubMed  Google Scholar 

  • Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM (1993) Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med 86:703–708

    CAS  PubMed  Google Scholar 

  • Kontic-Vucinic O, Sulovic N, Radunovic N (2006) Micronutrients in women's reproductive health: I. Vitamins. Int J Fertil Womens Med 51:106–115

    CAS  PubMed  Google Scholar 

  • Kühne T, Bubl R, Baumgartner R (1991) Maternal vegan diet causing a serious infantile neurological disorder due to vitamin-B12 deficiency. Eur J Pediatr 150:205–208

    PubMed  Google Scholar 

  • Larsson CL, Johansson GK (1997) Prevalence of vegetarianism in Swedish secondary schools. Scand J Nutr 41:117–120

    Google Scholar 

  • Larsson CL, Johansson GK (2002) Dietary intake and nutritional status of young vegans and omnivores in Sweden. Am J Clin Nutr 76:100–106

    CAS  PubMed  Google Scholar 

  • Leung S, Mattman A, Snyder F, Kassam R, Meneilly G, Nexo E (2010) Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem doi:10.1016/j.clinbiochem.2010.02.011

    PubMed  Google Scholar 

  • Lildballe DL, Hardlei TF, Allen LH, Nexo E (2009) High concentrations of haptocorrin interfere with routine measurement of cobalamins in human serum and milk. A problem and its solution. Clin Chem Lab Med 47:182–187

    CAS  PubMed  Google Scholar 

  • Louwman MW, van Dusseldorp M, van de Vijver FJ et al (2000) Signs of impaired cognitive function in adolescents with marginal cobalamin status. Am J Clin Nutr 72:762–769

    CAS  PubMed  Google Scholar 

  • Lovblad K, Ramelli G, Remonda L, Nirkko AC, Ozdoba C, Schroth G (1997) Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings. Pediatr Radiol 27:155–158

    CAS  PubMed  Google Scholar 

  • Magera MJ, Helgeson JK, Matern D, Rinaldo P (2000) Methylmalonic acid measured in plasma and urine by stable-isotope dilution and electrospray tandem mass spectrometry. Clin Chem 46:1804–1810

    CAS  PubMed  Google Scholar 

  • Mannino ML, Lee Y, Mitchell DC, Smiciklas-Wright H, Birch LL (2004) The quality of girls' diets declines and tracks across middle childhood. Int J Behav Nutr Phys Act 1:5

    PubMed  Google Scholar 

  • McLean ED, Allen LH, Neumann CG et al (2007) Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods. J Nutr 137:676–682

    CAS  PubMed  Google Scholar 

  • McPhee AJ, Davidson GP, Leahy M, Beare T (1988) Vitamin B12 deficiency in a breast fed infant. Arch Dis Child 63:921–923

    CAS  PubMed  Google Scholar 

  • Milman N, Byg KE, Bergholt T, Eriksen L, Hvas AM (2006) Cobalamin status during normal pregnancy and postpartum: a longitudinal study comprising 406 Danish women. Eur J Haematol 76:521–525

    CAS  PubMed  Google Scholar 

  • Minet JC, Bisse E, Aebischer CP, Beil A, Wieland H, Lutschg J (2000) Assessment of vitamin B-12, folate, and vitamin B-6 status and relation to sulfur amino acid metabolism in neonates. Am J Clin Nutr 72:751–757

    CAS  PubMed  Google Scholar 

  • Molloy AM, Mills JL, McPartlin J, Kirke PN, Scott JM, Daly S (2002) Maternal and fetal plasma homocysteine concentrations at birth: the influence of folate, vitamin B12, and the 5, 10-methylenetetrahydrofolate reductase 677C–>T variant. Am J Obstet Gynecol 186:499–503

    CAS  PubMed  Google Scholar 

  • Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL (2008) Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull 29:S101–S111, discussion S112–105

    PubMed  Google Scholar 

  • Monsen AL, Refsum H, Markestad T, Ueland PM (2003) Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years. Clin Chem 49:2067–2075

    CAS  PubMed  Google Scholar 

  • Murphy MM, Molloy AM, Ueland PM et al (2007) Longitudinal study of the effect of pregnancy on maternal and fetal cobalamin status in healthy women and their offspring. J Nutr 137:1863–1867

    CAS  PubMed  Google Scholar 

  • Northstone K, Emmett P, Nethersole F (2001) The effect of age of introduction to lumpy solids on foods eaten and reported feeding difficulties at 6 and 15 months. J Hum Nutr Diet 14:43–54

    CAS  PubMed  Google Scholar 

  • Obarzanek E, Hunsberger SA, Van Horn L et al (1997) Safety of a fat-reduced diet: the Dietary Intervention Study in Children (disc). Pediatrics 100:51–59

    CAS  PubMed  Google Scholar 

  • Osganian SK, Stampfer MJ, Spiegelman D et al (1999) Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health. Jama 281:1189–1196

    CAS  PubMed  Google Scholar 

  • Ozer EA, Turker M, Bakiler AR, Yaprak I, Ozturk C (2001) Involuntary movements in infantile cobalamin deficiency appearing after treatment. Pediat Neurol 25:81–83

    CAS  PubMed  Google Scholar 

  • Park MH, Kinra S, Ward KJ, White B, Viner RM (2009) Metformin for obesity in children and adolescents: a systematic review. Diab Care 32:1743–1745

    CAS  Google Scholar 

  • Patel KD, Lovelady CA (1998) Vitamin B12 status of East Indian vegetarian lactating women living in the United States. Nutr Res 18:1839–1846

    CAS  Google Scholar 

  • Pathak A, Godwin HA (1972) Vitamin B 12 and folic acid values in premature infants. Pediatrics 50:584–589

    CAS  PubMed  Google Scholar 

  • Rasmussen K, Moller J, Lyngbak M, Pedersen AM, Dybkjaer L (1996) Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation. Clin Chem 42:630–636

    CAS  PubMed  Google Scholar 

  • Rasmussen SA, Fernhoff PM, Scanlon KS (2001) Vitamin B12 deficiency in children and adolescents. J Pediatr 138:10–17

    CAS  PubMed  Google Scholar 

  • Ray JG, Blom HJ (2003) Vitamin B12 insufficiency and the risk of fetal neural tube defects. QJM 96:289–295

    CAS  PubMed  Google Scholar 

  • Refsum H, Wesenberg F, Ueland PM (1991) Plasma homocysteine in children with acute lymphoblastic leukemia. Changes during a chemotherapeutic regimen including methotrexate. Cancer Res 51:828–835

    CAS  PubMed  Google Scholar 

  • Requejo AM, Ortega RM, Navia B, Gaspar MJ, Quintas E, Lopez-Sobaler A (1997) Folate and vitamin B12 status in a group of preschool children. Int J Vitam Nutr Res 67:171–175

    CAS  PubMed  Google Scholar 

  • Rosenblatt DS, Cooper BA (1990) Inherited disorders of vitamin B12 utilization. Bioessays 12:331–334

    CAS  PubMed  Google Scholar 

  • Rosenblatt DS, Whitehead VM (1999) Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol 36:19–34

    CAS  PubMed  Google Scholar 

  • Ruscin JM, Page RL, Valuck RJ (2002) Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother 36:812–816

    PubMed  Google Scholar 

  • Sabatino D, Kosuri S, Remollino A, Shotter B (1998) Cobalamin deficiency presenting with cutaneous hyperpigmentation: a report of two siblings. Pediatr Hematol Oncol 15:447–450

    CAS  PubMed  Google Scholar 

  • Schneede J, Ueland PM, Kjaerstad SI (2003) Routine determination of serum methylmalonic acid and plasma total homocysteine in Norway. Scand J Clin Lab Invest 63:355–367

    CAS  PubMed  Google Scholar 

  • Scott JM (1999) Folate and vitamin B12. Proc Nutr Soc 58:441–448

    CAS  PubMed  Google Scholar 

  • Simsek OP, Gonc N, Gumruk F, Cetin M (2004) A child with vitamin B12 deficiency presenting with pancytopenia and hyperpigmentation. J Pediatr Hematol Oncol 26:834–836

    PubMed  Google Scholar 

  • Sneed SM, Zane C, Thomas MR (1981) The effects of ascorbic acid, vitamin B6, vitamin B12, and folic acid supplementation on the breast milk and maternal nutritional status of low socioeconomic lactating women. Am J Clin Nutr 34:1338–1346

    CAS  PubMed  Google Scholar 

  • Specker BL, Black A, Allen L, Morrow F (1990a) Vitamin-B-12: low milk concentrations are related to low serum concentrations in vegetarian women and to methylmalonic aciduria in their Infants. Am J Clin Nutr 52:1073–1076

    CAS  PubMed  Google Scholar 

  • Specker BL, Brazerol W, Ho ML, Norman EJ (1990b) Urinary methylmalonic acid excretion in infants fed formula or human milk. Am J Clin Nutr 51:209–211

    CAS  PubMed  Google Scholar 

  • Stabler SP, Allen RH (2004) Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr 24:299–326

    CAS  PubMed  Google Scholar 

  • Stollhoff K, Schulte FJ (1987) Vitamin B12 and brain development. Eur J Pediatr 146:201–205

    CAS  PubMed  Google Scholar 

  • Surtees R, Leonard J, Austin S (1991) Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet 338:1550–1554

    CAS  PubMed  Google Scholar 

  • Taneja S, Bhandari N, Strand TA et al (2007) Cobalamin and folate status in infants and young children in a low-to-middle income community in India. Am J Clin Nutr 86:1302–1309

    CAS  PubMed  Google Scholar 

  • ter Heide H, Hendriks HJ, Heijmans H et al (2001) Are children with cystic fibrosis who are treated with a proton-pump inhibitor at risk for vitamin B(12) deficiency? J Pediatr Gastroenterol Nutr 33:342–345

    PubMed  Google Scholar 

  • Tolia V, Boyer K (2008) Long-term proton pump inhibitor use in children: a retrospective review of safety. Dig Dis Sci 53:385–393

    CAS  PubMed  Google Scholar 

  • Ubbink JB, Becker PJ, Vermaak WJ, Delport R (1995) Results of B-vitamin supplementation study used in a prediction model to define a reference range for plasma homocysteine. Clin Chem 41:1033–1037

    CAS  PubMed  Google Scholar 

  • van Dusseldorp M, Schneede J, Refsum H et al (1999) Risk of persistent cobalamin deficiency in adolescents fed a macrobiotic diet in early life. Am J Clin Nutr 69:664–671

    PubMed  Google Scholar 

  • Vogiatzoglou A, Oulhaj A, Smith AD et al (2009) Determinants of plasma methylmalonic acid in a large population: implications for assessment of vitamin B12 status. Clin Chem 55:2198–2206

    CAS  PubMed  Google Scholar 

  • von Schenck U, Bender-Gotze C, Koletzko B (1997) Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy. Arch Dis Child 77:137–139

    Google Scholar 

  • Weir DG, Keating S, Molloy A et al (1988) Methylation deficiency causes vitamin B12-associated neuropathy in the pig. J Neurochem 51:1949–1952

    CAS  PubMed  Google Scholar 

  • Weir DG, Molloy A, Keating JN et al (1990) Hypomethylation produces vitamin B12 associated neuropathy in the pig. Biomedicine and Physiology of vitamin B-12. The Children’s Medical Charity, London, pp 129–151

  • Whitehead VM (2006) Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol 134:125–136

    CAS  PubMed  Google Scholar 

  • Whorton JC (1994) Historical development of vegetarianism. Am J Clin Nutr 59:1103S–1109S

    CAS  PubMed  Google Scholar 

  • Wighton MC, Manson JI, Speed I, Robertson E, Chapman E (1979) Brain damage in infancy and dietary vitamin B12 deficiency. Med J Aust 2:1–3

    CAS  PubMed  Google Scholar 

  • Wile DJ, Toth C (2010) Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diab Care 33:156–161

    CAS  Google Scholar 

  • World Health Organization (2001) The optimal duration of exclusive breastfeeding. Report of an expert consultation. World Health Organization, Geneva

    Google Scholar 

  • Worthingtonwhite DA, Behnke M, Gross S (1994) Premature infants require additional folate and vitamin B-12 to reduce the severity of the anemia of prematurity. Am J Clin Nutr 60:930–935

    CAS  Google Scholar 

  • Wright JD, Bialostosky K, Gunter EW et al (1998) Blood folate and vitamin B12: United States, 1988–94. Vital Health Stat 11:1–78

    Google Scholar 

  • Yavuz H (2008) Vitamin B(12) deficiency, seizure, involuntary movements. Seizure 17:748–749

    PubMed  Google Scholar 

  • Zengin E, Sarper N, Caki Kilic S (2009) Clinical manifestations of infants with nutritional vitamin B deficiency due to maternal dietary deficiency. Acta Paediatr 98:98–102

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway

    Anne-Lise Bjørke-Monsen & Per Magne Ueland

  2. Section of Pharmacology, Institute of Medicine, University of Bergen, Bergen, Norway

    Per Magne Ueland

Authors
  1. Anne-Lise Bjørke-Monsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Per Magne Ueland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne-Lise Bjørke-Monsen.

Additional information

Communicated by: Henk Blom

Competing interest: None declared.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bjørke-Monsen, AL., Ueland, P.M. Cobalamin status in children. J Inherit Metab Dis 34, 111–119 (2011). https://doi.org/10.1007/s10545-010-9119-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-010-9119-1

Keywords

Search

Navigation