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


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 micromol/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.


CONCLUSIONS
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).
Baggot
Paddy Jim
PJ
Queen of Angels Hospital, Los Angeles, CA, USA. pjbaggot@hotmail.com
Eliseo
Anna Jane Y
AJ
Kalamarides
Jeremy A
JA
Shoemaker
James D
JD
D000649:Amniocentesis; D000653:Amniotic Fluid / Q000378:metabolism*; D004314:Down Syndrome / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005565:Formiminoglutamic Acid / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy
D005565:Formiminoglutamic Acid; D005492:Folic Acid