ABSTRACT
A metabolomic analysis of plasma amino acids and acylcarnitines was applied to four disorders of nucleotide metabolism. Multivariate analysis gave score plots that show segregation of hypoxanthine phosphoribosyltransferase and adenine phosphoribosyltransferase deficient plasma from controls with equivocal results for adenosine deaminase and dihydropyrimidine dehydrogenase deficiencies. Loadings plots revealed the principal metabolites responsible for the discrimination between these classes. There were increases for HPRT in C4-, C6-, and C3-DC (malonyl)-carnitines, and decreased serine. For APRT there were increases in C4- to C10- and C3-DC to C6-DC-carnitines, urea, 1-methylhistidine, 3-methylhistidine, and decreased tryptophan. For ADA deficiency there were increases in C4- and C6-carnitines, taurine, and isoleucine.
Subject(s)
Metabolic Diseases/metabolism , Nucleotides/metabolism , Adenine Phosphoribosyltransferase/deficiency , Adenine Phosphoribosyltransferase/metabolism , Adenosine Deaminase/deficiency , Adenosine Deaminase/metabolism , Amino Acids/blood , Carnitine/analogs & derivatives , Carnitine/blood , Dihydropyrimidine Dehydrogenase Deficiency , Dihydrouracil Dehydrogenase (NADP)/metabolism , Genetic Diseases, Inborn/metabolism , Humans , Hypoxanthine Phosphoribosyltransferase/deficiency , Hypoxanthine Phosphoribosyltransferase/metabolism , Ninhydrin/metabolismABSTRACT
A media has been developed which enables the assessment of mitochondrial function in fibroblasts by measuring proliferation as an end point.
