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Cobalamin Status and Its Biochemical Markers Methylmalonic Acid and Homocysteine in Different Age Groups from 4 Days to 19 Years

¹ Department of Pediatrics and² Department of Pharmacology, and³ LOCUS for Homocysteine and Related Vitamins, University of Bergen, N-5021 Bergen, Norway.
⁴ Department of Pharmacology, University of Oxford, Oxford, UK.

^aAddress correspondence to this author at: Department of Pediatrics, Haukeland University Hospital, N-5021 Bergen, Norway. Fax 47-55-975147; e-mail albm{at}online.no.

Background: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year.

Methods: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years.

Results: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 µmol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3–7 years and then decreased, median plasma MMA remained low (<0.26 µmol/L), median plasma tHcy was low (<6 µmol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r = -0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r = -0.52) but not to serum folate in infants 6 months. In older children, tHcy showed the expected association with both cobalamin (r = -0.48) and folate (r = -0.51).

Conclusions: In infants 6 weeks to 6 months, concentrations of the metabolic markers MMA and tHcy were higher than in the other age groups and strongly correlated to cobalamin, whereas in older children, both makers showed correlations to cobalamin and folate concentrations documented in adults. Whether this metabolic profile in infants is explained by impaired cobalamin status, which in turn may have long-term effects on psychomotor development, remains to be addressed in intervention studies.

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