Search

Objective: Down's syndrome (DS) is the most frequent genetic cause of Alzheimer-type dementia. Its metabolic phenotype involves an increased trans-sulphuration of homocysteine. The aim of the present study was to investigate the influence of homocysteinaemia (t-Hcys), folate, vitamin B12, and related polymorphisms on intelligence quotient (IQ) in DS. Methods: The IQ of 131 patients with trisomy 21 from a specialist centre in Sicily was determined and classified according to DMS-IV. The effects of age, folate, vitamin B12, t-Hcys, and genetic polymorphisms on IQ were evaluated separately and in combination using regression analyses. Results: IQ was significantly lower in DS patients with t-Hcys >7.5 µmol/l (median) and in those who were carriers of methylenetetrahydrofolate reductase (MTHFR) 677 T allele and of methylenetetrahydrofolate reductase 677 T and transcobalamin 776 G combined alleles (p = 0.0013, p = 0.0165, and p = 0.0074, respectively). The IQ correlated significantly with t-Hcys and folate in single and multiple regression analyses, independently of age. In addition, t-Hcys >9.6 µmol/l (upper quartile) was found to be associated with low IQ (

Extensive evidence is presented that incubation of reduced Escherichia coli 13 vitamin-B 12 transmethylase with N 5 -methyl- 14 C-tetrahydrofolate (plus unlabeled S -adenosylmethionine), with methyl- 14 C- S -adenosyImethionine alone, or with methyl- 14 C iodide resulted in the formation of a methyl- 11 C -cobalamin enzyme. Under optimal conditions N 5 -methyl- 14 C -tetrahydrofolate and methyl- 14 C-S-adenosylmethionirie yielded 0.5 equivalent and 1 equivalent, respectively, of melhyl- 14 C-cobalamin enzyme. Unlabeled N 5 -methyletrahydrofolate decreased methyl- 14 C-B 12 enzyme formation with methyl- 14 C- S -adenosylmethionine by 10-fold. Methyl- 14 C-cobalamin enzyme formation was accompanied by changes in the absorption spectrum of the initial transmethylase and produced a spectrum that displayed the characteristic of free methylcobalamin. Upon the addition of homocysteine to a methyl- 14 C-cobalamin enzyme, methionine- 14 CH 3 was obtained and the spectrum reverted back to one which was similar to that for the original enzyme. Regardless of the methyl- 14 C group donor, the methyl- 14 C-cobalamin enzyme which formed was stable to light at 0 ° unless the protein solution was acidified to pH 2.