Jerome LeJeune is credited with the discovery that three 21 chromosomes caused Down syndrome (DS).  He also is credited with the discovery that DS people could not adequately process single carbon atom chains....today we know this is due to the disruption of the S-Adenosylmethionine cycle or SAM cycle which is mediated by the enzyme cystathionine beta synthase.  It is the enzyme cystathionine beta synthase that is overexpressed on the 21st chromosome....this means that there are three copies of this enzyme that cause a decrease in the amino acid cysteine pool, loss of homocysteine and a decrease in the methyl groups available for DNA methylation and other biomethylations.

    There is also an associated disruption of folic acid metabolism caused by a trapping of folate as 5-methyltetrahydrofolate.

    LeJeune also demonstrated abnormalities in the synthesis of purines that produced high uric acid in DS.  This action seems to be mediated through the GART gene which also is located on the 21st chromosome and has three functioning copies.