IN-VIVO FOLIC-ACID SUPPLEMENTATION PARTIALLY CORRECTS IN-VITRO METHOTREXATE TOXICITY IN PATIENTS WITH DOWN-SYNDROME

Patients with Down syndrome have been found to have characteristic in vivo and in vitro methotrexate toxicity. The in vitro methotrexate tox icity characteristic of Down syndrome can be diminished by the in vivo administration of supplemental high doses of folic acid. A possible e xplanation for the increased sensitivity to methotrexate which has bee n documented in patients with Down syndrome may be due to imbalances i n nucleotide pools which result from a gene dosage effect and to great er methylation demands. Supplemental folic acid may be beneficial by v irtue of a down-regulation of excess gene activity and may also provid e needed monocarbons.