DO CRITERIA EXIST FROM URINARY ORGANIC-ACIDS TO DISTINGUISH BETA-OXIDATION DEFECTS

Dicarboxylic acids are excreted in high amounts in urine when mitochon drial beta-oxidation of fatty acids is impaired and when the metabolic flux through this pathway is increased such as in catabolic situation s. They are formed by microsomal omega-oxidation of saturated, unsatur ated and 3-hydroxy monocarboxylic acids of different chain lengths for med at each step of the beta-oxidation spiral. The structure of the di carboxylic acids excreted should correspond to the specificity of the deficient enzyme towards its substrate (chain length and chemical stru cture of the acyl-CoA). In fact, the pattern of excretion is often mor e complex. On the other hand, dicarboxylic aciduria may arise in situa tions where hereditary defects of mitochondrial beta-oxidation of fatt y acids are not involved (starvation, medium-chain triglyceride (MCT) diet, valproate therapy, other metabolic diseases). We have retrospect ively analysed chromatographic profiles of urinary organic acids from patients with proven deficiencies of beta-oxidation and from patients with secondary dicarboxylic aciduria and tried to define criteria to d istinguish the defects of mitochondrial beta-oxidation of fatty acids from secondary disorders.