BIOCHEMICAL INVESTIGATIONS AND TRISOMY-21

  • 1 January 1979
    • journal article
    • research article
    • Vol. 22  (2) , 67-75
Abstract
A general study of the pathogenesis of metabolic diseases causing mental deficiency shows the importance of a disturbance in the 1-carbon cycle (or folate cycle). Reviewing the diseases that present some of the signs of trisomy 21 leads to the suspicion that the following anomalies may be involved: a collagen defect (hypothyroidism and iminopeptiduria); a metabolic oxygen defect (hypo thyroidism and hemoglobinopathies); a cholinergic defect (Alzheimer''s disease); and a 1-carbon cycle breakdown (Lesh-Nyhan disease). The pathology typical of trisomy-21 suggests a cholinergic defect and an aberration associated with the introduction of 10-formyltetrahydrofolate of the folic acid cycle. An analysis of the possible effects of excesses of superoxide dismutase A and an glutathione peroxidase suggests that there may be dioxygenation and nonaromatic hydroxylation problems and a relative inhibition of certain reactions with FAD. A simplified scheme shows that these metabolic deviations might engender collagen defects and disturbances of the synthesis of chemical mediators, as suggested by indications from comparative pathogenesis of the various disorders studied.