Lysinuric protein intolerance: reviewing concepts on a multisystem disease.

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.

Organic acidurias: a review. Part 2.

Laboratory findings are an essential part of the diagnostic approach to organic acidemias. In most organic acidemias, metabolism of glucose, ketone bodies, and ammonia is deranged primarily or secondarily, in addition to derangement of the acid-base balance. Hypoglycemia, lactic and/or ketoacidosis, and hyperammonemia of varying severity accompany the overt or compensated acidosis. In most instances, a definite diagnosis will be achieved by gas chromatography/mass spectrometry (GC/MS) studies of the urine. We detail the pattern of excreted organic acids in the major disorders. When the diagnosis reached by clinical and laboratory assessments is not conclusive, it must be supported by loading tests. We list the available methods of demonstrating the putative enzyme deficiency in the patient's cells and tissues. The majority of organic acidemias may be treated by limiting the source of or removing the toxic intermediary metabolite. We provide lists of available diets, supplements, and medications. In some instances, residual defective enzyme activity may be stimulated. We describe symptomatic management of the disturbed acid-base and electrolyte balance.