title: [Pathogenesis of mental impairment in trisomy 21].
abstract: 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, and 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 biopterin metabolism interferences are reviewed. These metabolic paths are tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutual regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate, and 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. Re-equilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo Alzheimer complication is presented.
authors.affiliation: Centre de Recherches Claude-Bernard, Génétique Humaine et Maladies de l'Intelligence, Institut de Progenèse, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Lejeune
mesh_terms: D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000502:physiology; D004314:Down Syndrome / Q000188:drug therapy / Q000523:psychology*; D006801:Humans; D066298:In Vitro Techniques; D008607:Intellectual Disability / Q000188:drug therapy / Q000235:genetics*
vernacular_title: Pathogénie de la débilité de l'intelligence dans la trisomie 21.