A folate-dependent metabolite in amniotic fluid from pregnancies with normal or trisomy 21 chromosomes

Introduction: Previous studies have given conflicting results as to whether or not folate metabolism is altered in Down syndrome. Folate is necessary to facilitate metabolism of one-carbon units. Folate accepts one-carbon units from one-carbon unit donors, including formiminoglutamate (FIGLU). Folate deficiency leads to accumulation of FIGLU and impairment of one-carbon unit metabolism. FIGLU is a functional measure of folate deficiency. Materials and Methods: Archived anonymized amniotic fluid specimens were obtained from normal pregnancies and those with Down syndrome. Gas liquid chromatography/mass spectrometry was used to quantitate FIGLU, which is elevated in folate deficiency. A tetra-deuterated FIGLU was used as a standard, and single-ion monitoring was performed. Nonparametric statistical analysis was performed with the Mann-Whitney U test. Results: FIGLU was significantly lower in pregnancies with Down syndrome. The median FIGLU level was 0.9 mu mol/l in amniotic fluid from fetuses with Down syndrome. The median FIGLU level was 1.3 in amniotic fluid from control fetuses. This difference was statistically significant (p = 0.009). No statistically significant differences were found with histidine or glutamate. Discussion: There was no evidence of folate deficiency. FIGLU was decreased, not increased. Decreased FIGLU might result from accelerated activity of one or more genes on chromosome 21, by a gene dosage effect. Genes which might explain the reduced FIGLU include one which degrades FIGLU (glutamate formiminotransferase-cyclodeaminase), one which participates in purine synthesis, and one which degrades homocysteine (cystathionine-beta-synthase). Copyright (c) 2006 S. Karger AG, Basel.