On the differences between urinary metabolite excretion and odd-numbered fatty acid production in propionic and methylmalonic acidaemias.
In five subjects with methylmalonic acidaemia (MMA) and five with propionic acidaemia (PA) both the level of odd-numbered fatty acids (OLCFA) in erythrocyte lipids and the excretion of propionate-derived metabolites in urine were longitudinally analysed. At a given intake of amino acid precursors of propionyl-CoA and otherwise stable metabolic conditions, subjects with MMA excreted considerably more propionate-derived metabolites, and accumulated less OLCFA in excretion erythrocyte lipids than subjects with PA. We suggest that renal metabolite excretion indicates the efflux of organic acids from cells and might be a measure of the individually determined intracellular relief from toxic acyl-CoA esters. It does not necessarily reflect the total amount of acyl-CoA intermediates produced in the body. OLCFA levels seem to reflect the continuous burden of propionyl-CoA toxicity within the cells and thereby might serve as a reliable tool for evaluating the quality of long-term metabolic control in these disorders.
Wendel
U
U
Kinderklinik, Heinrich-Heine-Universität Düsseldorf, Germany.
Eissler
A
A
Sperl
W
W
Schadewaldt
P
P
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D008055:Lipids / Q000097:blood; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood* / Q000652:urine*; D011422:Propionates / Q000097:blood* / Q000652:urine*
D005227:Fatty Acids; D008055:Lipids; D011422:Propionates; D008764:Methylmalonic Acid