ABSTRACT
Lysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective cationic amino acid transport at the basolateral membrane of epithelial cells in intestine and kidney. LPI is caused by mutations in the SLC7A7 gene, which encodes the y(+)LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family. LPI was initially described in Finland, but has worldwide distribution. Typically, symptoms begin after weaning with refusal of feeding, vomiting, and consequent failure to thrive. Hepatosplenomegaly, hematological anomalies, neurological involvement, including hyperammonemic coma are recurrent clinical features. Two major complications, pulmonary alveolar proteinosis and renal disease are increasingly observed in LPI patients. There is extreme variability in the clinical presentation even within individual families, frequently leading to misdiagnosis or delayed diagnosis. This condition is diagnosed by urine amino acids, showing markedly elevated excretion of lysine and other dibasic amino acids despite low plasma levels of lysine, ornithine, and arginine. The biochemical diagnosis can be uncertain, requiring confirmation by DNA testing. So far, approximately 50 different mutations have been identified in the SLC7A7 gene in a group of 142 patients from 110 independent families. No genotype-phenotype correlation could be established. Therapy requires a low protein diet, low-dose citrulline supplementation, nitrogen-scavenging compounds to prevent hyperammonemia, lysine, and carnitine supplements. Supportive therapy is available for most complications with bronchoalveolar lavage being necessary for alveolar proteinosis.
Subject(s)
Kidney/metabolism , Lysine/urine , Renal Aminoacidurias/genetics , Renal Aminoacidurias/metabolism , Amino Acid Transport System y+L , Amino Acid Transport Systems/genetics , Amino Acid Transport Systems, Basic/genetics , Amino Acid Transport Systems, Basic/metabolism , Epithelial Cells/metabolism , Finland , Fusion Regulatory Protein 1, Light Chains/genetics , Fusion Regulatory Protein 1, Light Chains/metabolism , Genetic Association Studies , Humans , Intestinal Mucosa/metabolism , Large Neutral Amino Acid-Transporter 1/genetics , Mutation , Pulmonary Alveolar Proteinosis/genetics , Pulmonary Alveolar Proteinosis/metabolism , Renal Aminoacidurias/diagnosis , Renal Aminoacidurias/diet therapySubject(s)
Amino Acid Metabolism, Inborn Errors , Nutritional Physiological Phenomena , Adult , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/diet therapy , Child , Cystinuria/diet therapy , Dietary Proteins/metabolism , Female , Hartnup Disease/diet therapy , Homocystinuria/diet therapy , Humans , Infant, Newborn , Male , Maple Syrup Urine Disease/diet therapy , Nutritional Requirements , Phenylketonurias/diet therapy , Pregnancy , Renal Aminoacidurias/diet therapy , VitaminsABSTRACT
A patient with a Lowe syndrome was observed from birth. Progressive hyperchloraemic renal tubular acidosis, hypophosphataemia, hyperphosphaturia and generalized hyperaminoaciduria had developed in infancy. Supplementary vitamin D, alkali and a high intake of dietary phosphate were unsuccessful in controlling the severe phosphate diabetes and rickets. Contraction of the extracellular fluid volume by dietary sodium restriction resulted in correction of the acidosis, hypophosphataemia, hyperaminoaciduria, and hyperphosphaturia, and healing of the rickets.
