Free amino acids in extracts of cultured skin fibroblasts from patients with various amino acid metabolic disorders

In the search for a simple screening test for prenatal diagnosis of amino acid metabolic disorders, we compared the free amino acid contents in the extract of cultured skin fibroblasts from normal individuals with that from patients with 10 metabolic disorders: maple-syrup urine disease; homocystinuria due to cystathionine synthase deficiency; homo-cystinuria due to N5,10--methylene-tetrahydrofolate reductase deficiency; citrullinemia; argininosuccinic acidemia; propionic acidemia; hyperprolinemia Type II; non-ketotic hyper-glycinemia; hydroxyprolinemia; and hyperornithinemia. An accumulation of abnormal metabolites was not found in any of the disorders except argininosuccinic aciduria. Argininosuccinic acid anhydrides were detected in cell extracts from all four patients only after the extract was boiled at acid pH for 21/2 h. Thus, it is concluded that the measurement of free amino acids in extracts from cultured fibroblasts is not a useful screening technique in the diagnosis of inborn errors of amino acid metabolism.