Hyperhomocysteinemia and B-Vitamin Deficiencies in Infants and Children

Abstract

Measurement of total homocysteine (tHcy) in healthy and diseased children has documented the utility of this marker in pediatric research and diagnostics. This article focuses on novel data obtained in infants, children and adolescents, with emphasis on cobalamin status in infants. In children, determinants of plasma tHcy are similar to those established in adults, and include age, gender, nutrition, B-vitamin status, and some drugs interfering with B-vitamin function. In infants (age < 1 year), tHcy is moderately elevated and related to serum cobalamin, whereas in older children and throughout childhood, plasma tHcy is low (about 60% of adult levels), and folate status becomes a strong tHcy determinant. As in adults, hyperhomocysteinemia in childhood is a risk factor for stroke, and folate-responsive hyperhomocysteinemia has been detected in children with renal failure. tHcy seems to be a sensitive indicator of folate deficiency in children on a poor diet, in HIV-infected children, and in children treated with anti-folate drugs. In children at increased risk of cobalamin deficiency, which includes children born to vegetarian mothers or children in developing countries on a poor diet, tHcy and methylmalonic acid are responsive indicators of a deficiency state. In newborns and infants born to mothers with an adequate nutrition, there are consistent observations of low cobalamin, elevated tHcy and methylmalonic acid, and reduction of both metabolites by cobalamin supplementation. These data have raised the question whether cobalamin deficiency may be widespread and undetected in babies born to non-vegetarian women on a Westernized diet.

Screening for Serum Total Homocysteine in Newborn Children

“…However, even in babies with serum folate Ͻ5 nmol/L (approximately the 1st percentile), the TT genotype had no effect on tHcy. It has been suggested that high serum folate during infancy is attrib- utable to low B 12 status and the resulting methyl folate trap phenomenon (16,17 ). Another, and more likely, cause is that the supply of folate is high via the placenta (51 ) and in breast milk (52,53 ).…”

“…Such neonatal B 12 deficiency is nearly always attributable to low maternal B 12 status (16 ). These babies already have low B 12 combined with increased concentrations of tHcy and the specific B 12 marker, methylmalonic acid (MMA; Fig.…”

“…They continue to have a low B 12 status during infancy, particularly if the baby is exclusively breastfed (13,17,18 ). B 12 deficiency may lead to failure to thrive and developmental delay in infancy and lower cognitive function later in childhood (16 ). Low B 12 status is usually easily corrected by supplying vitamin B 12 (19 ).…”

Contribution of food sources to the vitamin B12 status of South Indian children from a birth cohort recruited in the city of Mysore

“…We also examined whether intakes of traditional Indian fermented foods (whose preparation involves microbial activity) and of raw vegetables (that may be contaminated with bacteria) were associated with higher B 12 concentrations. Maternal B 12 status is correlated with neonatal B 12 status (19,27,28) . We therefore assessed whether maternal B 12 concentrations in plasma samples collected during the pregnancy of each child were related to children's B 12 concentrations at 9·5 years.…”

A longitudinal study of serum cobalamins and its binding proteins in lactating women

“…In most cases, an apparent vitamin B 12 deficiency may be attributed to a low vitamin B 12 status in the mother (Specker et al, 1988Casterline et al, 1997;Ueland and Monsen 2003). These observations suggest that lactating mother do not have a sufficient intake of vitamin B 12 to ensure the needs of both the mother and the baby and emphasize the need to examine the status of cobalamin and its binding proteins in lactating mothers.…”