oxalates and Intellectual-Disability

A general consideration of the pathogenesis of the various metabolic diseases which produce mental deficiency suggests that perturbation of the one carbon (folate) cycle may be important. Secondly, a review of diseases having some symptoms in common with trisomy 21 suggests the evidence of : a collagen disturbance (hypothyroidism and iminodipeptidurial) ; an oxygen disturbance (hypothyroidism and hemoglobinopathies) ; a cholinergic distrubance (Alzheimer's disease) ; a one-carbon-cycle disturbance (Lesch-Nyhan's disease). Thirdly, the peculiar pathology of trisomy 21 allows to find also a cholinergic disturbance and a disturbance close to the 10 formyl-tetrahydrololate entry of the folate cycle. Finally, an analysis of the possible effect of the excess of superoxide dismutase A and of the increase of glutathion peroxidase leads to the suspicion that a difficulty exists of dioxygenations and of non aromatic hydroxilations with a relative retardation of some FAD requiring reactions. A simplified scheme shows that these metabolic deviations could provoke a disturbance of the collagen and of synthesis of chemical mediators, in accordance with the indications furnished by the compared pathogenesis of the various affections studied. These heuristic reflexions open the way to further investigations.

Topics: Down Syndrome; Folic Acid; Glyoxylates; Humans; Hydrogen Peroxide; Intellectual Disability; Oxalates; Superoxides; Thiamine; Tryptophan

Hydroxyproline metabolism was evaluated in two sisters with hydroxyprolinemia and their mother. 33 and 21% of an oral hydroxyproline load (200 mg/kg) was excreted by the sisters, 5.4% by the mother, and 1.3% by normal subjects. Plasma and erythrocyte values in the sisters and their mother were elevated, indicating that extra- and intracellular hydroxyproline pools were increased. Analysis for urinary glycolate and oxalate (metabolic products of hydroxyproline) showed no increased excretion by the two sisters, although the mother's excretion was normal. A deficiency of hydroxyproline oxidase in the two sisters was indicated by the lack of delta 1-pyrroline-3-hydroxy-5-carboxylic acid excretion.

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Female; Glycolates; Humans; Hydroxyproline; Intellectual Disability; Male; Middle Aged; Oxalates; Oxidoreductases

Topics: Amino Acid Metabolism, Inborn Errors; Animals; Erythrocytes; Female; Glycine; Glyoxylates; Humans; Infant; Infant, Newborn; Intellectual Disability; Kidney; Liver; Male; Myocardium; Oxalates; Oxidoreductases; Rats; Seizures

Topics: Amino Acid Metabolism, Inborn Errors; Blood; Cerebrospinal Fluid; Child, Preschool; Chromatography; Glycine; Humans; Infant; Intellectual Disability; Male; Oxalates; Sweat; Urine

Topics: Alanine; Brain Diseases; Child; Humans; Hyperglycemia; Hyperoxaluria; Infant; Intellectual Disability; Metabolic Diseases; Oxalates; Urine