Pathogenesis of mental deficiency in trisomy 21.
In trisomy 21, pathogenesis of mental retardation is still poorly understood although the knowledge of the genic content of chromosome 21 is steadily increasing. Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially. A biochemical scheme of impairment of mental efficiency is presented. Secondarily, the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S 100 beta protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterine metabolism interferences are reviewed. It is observed that the metabolic paths controlled by these genes, although unrelated at first glance, are in fact tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutually controlled regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate. From this starting point, systematic research of special sensitivities has begun. Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Reequilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo-Alzheimer complication is presented.
Lejeune
J
J
Centre de Recherches Claude Bernard, Génétique Humaine et Maladies de l'Intelligence, Institut de Progenèse, Paris, France.
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005796:Genes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology
D008727:Methotrexate