Elevated serum S-adenosylhomocysteine in cobalamin-deficient megaloblastic anemia.

Impaired methylation due to accumulation of S-adenosylhomocysteine (SAH) may contribute to the pathophysiology of cobalamin-deficient anemia. We assayed serum S-adenosylmethionine (SAM), SAH, total homocysteine (tHcy), and methylmalonic acid (MMA) in 15 subjects with cobalamin-deficient megaloblastic anemia and compared results with those of 19 subjects with anemia/pancytopenia due to other causes. Cobalamin-deficient subjects had a median hematocrit level of 20% and mean cell volume of 111.7 fL. The median serum cobalamin level was 37 pg/mL, MMA 3030 nmol/L, and tHcy 62.0 micromol/L. SAH was elevated in 13 of 15 subjects (median, 42 nmol/L) and the median SAM value was normal (103 nmol/L), but SAM/SAH ratio was low (2.5). The SAH was higher and SAM/SAH ratio was lower in cobalamin-deficient subjects compared with those with other anemias after excluding 4 patients with renal insufficiency. SAM concentrations were not low in cobalamin deficiency. Cobalamin injections corrected anemia, MMA, tHcy, SAM/SAH ratio, and SAH. Some hematologic variables were inversely correlated with SAH and cobalamin but not tHcy or MMA. In conclusion, serum SAH is elevated in cobalamin-deficient subjects with megaloblastic anemia and corrects with parenteral cobalamin therapy.

Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns.

BACKGROUND: Pregnant women with low cobalamin concentrations are unable to provide the necessary amount of cobalamin to their fetuses. The effect of low maternal cobalamin concentrations on transmethylation metabolism in pregnant women and their newborns is unknown. OBJECTIVE: We investigated the relation between maternal and neonatal cobalamin concentrations and changes in total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). DESIGN: Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery. RESULTS: The tHcy concentrations were higher in placental vein serum from newborns whose mothers had low cobalamin. Serum SAH concentrations were elevated and serum SAM and methionine concentrations were decreased in pregnant women with lower cobalamin concentrations. SAM:SAH was significantly decreased in both cobalamin-deficient pregnant women and their newborns. CONCLUSIONS: Lower maternal cobalamin concentrations are associated with higher tHcy and lower SAM:SAH in newborns. Because SAM:SAH is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation could be impaired in cobalamin-deficient pregnant women and their newborns.