Argininosuccinic aciduria, an inborn error of amino acid metabolism.

It is probable that many, if not all, of the inherited ('inborn') metabolic disturbances result from a specific enzyme defect, arising from a single abnormal gene. Examples are now known of a number of such inherited defects, some involving amino acids, which result in a block of a metabolic pathway. For example, the normal pathway for the metabolism of phenylalanine and tyrosine is by a series of conversions, each mediated by a specific enzyme. The lack of any one of these enzymes will lead to a specific disease and at least four such diseases have been identified, the most common of which is phenylketonuria. Similar enzyme deficiencies involving the metabolism of amino acids are, however, still very uncommon. A new instance has been recorded by Allan, Cusworth, Dent and Wilson (1958). They have described two sibs, suffering from mental retardation, who excreted in the urine large amounts of an amino acid not normally present. Later Westall (1960a, b) identified this substance as argininosuccinic acid, a known intermediate in the bio-synthesis of urea. The condition must be rare, since Allan et al. (1958) stated that 1,500 mentally deficient patients were screened and no further examples discovered. This paper records an infant with an identical abnormality, detected within a month of birth in December 1958, and the only other example of this type so far described. A metabolic disorder was suspected because clinical examination and routine pathological investigations had revealed no obvious cause for a sudden onset of severe illness in the first week of life. Paper chromatography of the urine showed a gross amino aciduria due to the presence of large amounts ofan amino acid and some progress had been made towards identifying the amino acid before the article by Allan et al. (1958) was noted. The similarity between the properties of the amino acids in their cases and ours led us to suspect that they were identical, and this was later proved by comparison with a specimen of argininosuccinic acid (ASA) isolated from the published cases and kindly provided by Dr. Westall. The detrimental effect on this infant of his metabolic disorder, and the history of the two earlier cases, indicated the desirability of early investigations which might provide a pointer for rational dietetic therapy such as that now in use in certain other inherited metabolic disturbances. Some such investigations are described in this paper, but so far they have not paved the way for treatment.