Argininosuccinic aciduria: identification and reactions of the abnormal metabolite in a newly described form of mental disease, with some preliminary metabolic studies

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Abstract
The unknown metabolite previously described as the predominant amino acid in the urine of 2 mentally defective sibs was isolated and proved to be argininosuccinic acid. The behavior of argininosuccinic acid in aqueous solution was studied. It apparently forms an equilibrium with 2 other modified forms which are probably cyclized anhydrides. The complicated behavior of argininosuccinic acid on resin columns can be explained on the basis of its known reactivity. It is, nevertheless, possible to assay it by the method of Moore and Stein (1954). Each patient with argininosuccinic aciduria excreted about 3 g of argininosuccinic acid per 24 hr. in his urine. Argininosuccinic acid and its 2 anhydride forms yield ornithine and aspartic acid after long hydrolysis with strong alkali, but with weaker alkali for a shorter time a number of intermediates are formed which include arginine and citrulline. An unknown substance was found in the urine of one patient with argininosuccinic aciduria which after treatment with strong alkali breaks down to yield aspartic acid and ornithine. The gross excretion 6f argininosuccinic acid seemed little affected by lowering the protein content of the diet over a short period or by adding arginine, but it was increased by feeding ornithine and citrulline.