The fact that citrate, aconitate, and isocitrate are all higher while all the other compounds in the TCA cycle are lower in T21 samples is consistent with a known mitochondrial defect in trisomy 21, in which several mitochondrial enzymes, including isocitrate dehydrogenase, show reduced activities.32 It was interesting, but unexpected, that lactose and 3′SL are detected in all amniotic fluid samples (case and control). This evidence concerns the gene IDH3A and trisomy 21.