Aminoaciduria and Glycosuria in Children

Abstract

Hereditary tubular transport disorders that lead to abnormal aminoaciduria and glycosuria are uncommon but are of major biologic importance. Some of these diseases can be associated with significant morbidity. In the past two decades, remarkable progress has been made in our understanding of the molecular pathogenesis of hereditary aminoaciduria and glycosuria. Molecular genetics and molecular biology studies have led to the identification of numerous mutations resulting in aminoaciduria and glycosuria, have provided important insight into the defective molecular mechanisms underlying these disorders, and have greatly increased our understanding of the physiology of renal tubular reclamation of amino acids and glucose. This chapter summarizes the general characteristics of proximal tubular transport of amino acids and glucose, discusses the specificity and classification of amino acid and glucose transport systems, reviews the molecular pathophysiology and genetic aspects of hereditary aminoaciduria and glycosuria, describes the clinical features of these tubulopathies, and summarizes their therapy. Special emphasis is given to cystinuria, lysinuric protein intolerance, Hartnup disease, iminoglycinuria, dicarboxylic aminoaciduria, familial renal glycosuria, and Fanconi-Bickel syndrome. Further molecular studies of inherited proximal tubular transport disorders resulting in aminoaciduria and glycosuria may shed more light on the molecular pathophysiology of these diseases and may significantly improve our understanding of the mechanisms underlying renal handling of amino acids and glucose in health and disease. The identification of the molecular defects in these inherited tubulopathies may provide a basis for future design of targeted therapeutic interventions for molecular therapy of these complex disorders.