The clinical significance of aminoaciduria

Abstract

Summary Hyperaminoaciduria is significant as a manifestation of aberrant cellular function in the kidney and in other organs (bone, liver, and brain in particular). The various patterns of hyperaminoaciduria may be described in terms of the endogenous renal clearances of the individual amino acids. Normally, those amino acids with the higher plasma concentrations or with the higher endogenous renal clearances or with both appear in the urine in the greater concentrations. The pattern of generalized renal aminoaciduria results when mechanisms common to the reabsorption of all amino acids are impaired. This pattern is nonspecific and may be seen in a variety of syndromes, the most common of which are the Fanconi syndrome and vitamin D deficiency states. Generalized renal hyperaminoaciduria may be distinguished from the generalized “overflow” aminoaciduria of severe hepatic cell damage and from the specific patterns of renal and systemic origin. A classification of aminoaciduria on this functional basis is presented. The finding of generalized renal hyperaminoaciduria in diseases of varied etiology suggests that this type of aminoaciduria is a very sensitive manifestation of impaired renal tubular function. Although the aminoaciduria results from renal injury, defects involving many organs may be present in these diseases. Indeed, cerebral and hepatic features may predominate the clinical picture in some of these diseases (e.g., galactosemia, lead encephalopathy, and Wilson's disease). The occurrence of the triad of renal aminoaciduria, glycosuria, and hypophosphatemia provides further evidence of an interrelationship between the renal tubular mechanisms for the reabsorption of these substances. Still other derangements of renal tubular function may be present when this triad is found. This emphasizes the need for complete studies of renal function in clinical problems in which any one discrete tubular function is obviously deranged. Distinctive “patterns of aminoaciduria” are found in various forms of rickets and osteomalacia. As the therapy differs in each, urinary amino acid studies may be helpful in therapeutic management. Likewise, specific patterns of aminoaciduria facilitate the accurate diagnosis of some forms of cerebral defect which have similar clinical features (e.g., phenylketonuria and “maple syrup urine disease”). The study of patterns of aminoaciduria has proved to be a valuable technique in genetic surveys and in the unraveling of obscure metabolic disorders in which the metabolism of individual amino acids and closely related intermediates is involved. As the technique of paper chromatography becomes more widely used, it may be anticipated that still other errors of intermediary metabolism will be identified among syndromes that are without distinctive clinical features. Semiquantitative paper chromatographic estimation of urinary acid patterns is adequate for most clinical problems in which aminoaciduria is suspected.