Aminoaciduria and Glycosuria in Children

Only negligible amounts of amino acids and glucose are normally present in the final urine, reflecting very efficient reabsorption mechanisms for these organic solutes in the proximal tubule. Renal tubular transport defects or specific metabolic abnormalities result in excretion of significant quantities of amino acids or glucose in the urine. Although hereditary defects in renal tubular transport of most of these substances are uncommon, they are of major biologic importance. First, some of these membrane transport disorders (e.g., cystinuria, lysinuric protein intolerance, Hartnup disease) are associated with significant morbidity. Second, the study of these disorders has provided much insight into the physiology of renal tubular reclamation of amino acids and glucose and into the specific metabolic pathways that control their reabsorption and has been crucial in understanding the genetics of tubular transport systems. This chapter summarizes the general characteristics of renal tubular transport of amino acids and glucose, outlines the two main classifications used for amino acid transport systems (based on chemical properties/substrate specificity and sequence homology), reviews recent studies on the molecular biology of the transporters, describes the ontogeny of these transport processes, and discusses the specific hereditary membrane transport disorders that result in abnormal aminoaciduria and glycosuria. Special emphasis is given to classic cystinuria, lysinuric protein intolerance, Hartnup disease, iminoglycinuria, and dicarboxylic aminoaciduria, including molecular genetic aspects of these diseases. Not discussed in this chapter are overflow aminoaciduria and glycosuria, which occur when the filtered load of these solutes exceeds the transport capacity of the renal tubule. This tubular overload is characteristic of various inborn errors of amino acid metabolism and diabetes mellitus, which result in elevated plasma levels of amino acids and glucose, respectively. Fanconi syndrome, a proximal tubular disorder characterized by generalized aminoaciduria, and urinary hyperexcretion of glucose, bicarbonate, phosphate, and other solutes, is discussed in separate chapters.