Diagnosis Of Lysinuric Protein Intolerance Research Articles

Early Diagnosis of Lysinuric Protein Intolerance: A Case Report

Introduction: Lysinuric protein intolerance (LPI) is a metabolic disorder resulting from recessive inherited mutations involving the SLC7A7 gene that control the transport of urea cycle intermediates. Case report: In this study we report a case of a kid who diagnosed with LPI at age of 18 month, he has recurrent vomiting and diarrhea with a break in the height-weight curve, the dosage of orotic acid in the urine which was increased, the chromatography of the amino acids which found a low level of lysine, ornithine and arginine in the blood and increased in the urine suggestive of LPI. Discussion: The defects occur in the y+ LAT1 sub-unit of the cationic amino acids transporter localized in the kidney and also expressed in the lung, spleen and in circulating monocytes and macrophages, which explain that an LPI patient usually comes with hepatosplenomegaly, failure to thrive, aversion to protein rich food, and poor feeding.

Renal Involvement in a French Paediatric Cohort of Patients with Lysinuric Protein Intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive metabolic disorder, caused by defective transport of cationic amino acids at the basolateral membrane of epithelial cells, typically in intestines and kidneys. The SLC7A7 gene, mutated in LPI patients, encodes the light subunit (y+LAT1) of a member of the heterodimeric amino acid transporter family.The diagnosis of LPI is difficult due to unspecific clinical features: protein intolerance, failure to thrive and vomiting after weaning. Later on, patients may present delayed growth osteoporosis, hepatosplenomegaly, muscle hypotonia and life-threatening complications such as alveolar proteinosis, haemophagocytic lymphohistiocytosis and macrophage activation syndrome. Renal involvement is also a serious complication with tubular and more rarely, glomerular lesions that may lead to end-stage kidney disease (ESKD). We report six cases of LPI followed in three different French paediatric centres who presented LPI-related nephropathy during childhood. Four of them developed chronic kidney disease during follow-up, including one with ESKD. Five developed chronic tubulopathies and one a chronic glomerulonephritis. A histological pattern of membranoproliferative glomerulonephritis was first associated with a polyclonal immunoglobulin deposition, treated by immunosuppressive therapy. He then required a second kidney biopsy after a relapse of the nephrotic syndrome; the immunoglobulin deposition was then monoclonal (IgG1 kappa). This is the first observation of an evolution from a polyclonal to a monotypic immune glomerulonephritis. Immune dysfunction potentially attributable to nitric oxide overproduction secondary to arginine intracellular trapping is a debated complication in LPI. Our results suggest all LPI patients should be monitored for renal disease regularly.

Neonatal lupus and a seronegative mother

A newborn baby girl had a diffuse vasculitic rash and mild hepatosplenomegaly. Her birthweight was 2·6 kg and her parents were healthy and unrelated. Prenatal screening for rubella, cytomegalovirus, toxoplasmosis, herpes, and HIV was reportedly negative. Blood tests showed increased transaminases. In May, 2000, at the age of 3 months, she was referred to us with a persistent rash (figure), stunted growth, and loss of appetite. Her weight was 4·020 kg. We examined her and found massive hepatosplenomegaly and hypotonia. Blood tests showed thrombocytopenia, anaemia, and increased lactate deyhdrogenase (LDH); 1729 U/L (84–362) and ferritin; 1219 ng/mL (7–85). Immunofluorescence of Hep2 cells showed antinuclear antibodies (ANA) at a titre of 1:320 with a speckled pattern. Extractable nuclear antigen profile showed antiRo-SSA, and Coombs’ test was negative. We suspected that the child had neonatal systemic lupus erythematosus. However, an ECG did not show any abnormalities, 1 and the mother had no ANA or anti-RoSSA/La-SSB antibodies. This finding was confirmed with two additional different assays. A bone marrow aspiration showed haemophagocytic lymphohistiocytosis. Because of the presence of hepatosplenomegaly, poor feeding, muscular hypotonia, high levels of ferritin and LDH, we then considered the diagnosis of lysinuric protein intolerance (LPI, McKusick 22700). We measured plasma and urine concentrations of lysine, arginine, and ornithine. All three aminoacids were below normal levels in the plasma, and above normal in the urine. We also measured high levels of orotic acid in a 24 h urine collection. The diagnosis of LPI was confirmed by molecular analysis of the SLC7A7 gene. 2

Feasibility of prenatal diagnosis of lysinuric protein intolerance by linkage analysis: a case report

Feasibility of prenatal diagnosis of lysinuric protein intolerance by linkage analysis: a case report

Feasibility of prenatal diagnosis of lysinuric protein intolerance by linkage analysis: a case report

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport (CAA), relatively common in Finland and Italy. After weaning, LPI patients present poor feeding, vomiting and failure to thrive. A severe pulmonary complication and episodes of metabolic imbalance may lead to death. Prenatal diagnosis has not been available due to lack of either biochemical or molecular markers to be used in the fetal period. The LPI locus has recently been assigned to chromosome 14q12, very close to the T-cell receptor alpha-chain (TCRA) locus. We carried out a prenatal diagnosis for LPI by linkage analysis in one LPI Italian family after CVS. For the haplotype analysis 11 DNA markers from the LPI critical region were used (D14S742, D14S50, D14S283, five TCRA intragenic polymorphic sites, D14S990, MYH7 and D14S80). It was concluded that the haplotype analysis indicated that the fetus was healthy as he had inherited the two wild alleles of the LPI locus. After birth, the clearances of CAA were measured and found to be in the normal range, thus confirming the result of the prenatal diagnosis. The prenatal diagnosis of LPI can now be offered to families affected by LPI.

Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance

We describe 4 cases of lysinuric protein intolerance, which all fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. Mature histiocytes and neutrophil precursors participated in hemophagocytosis in the bone marrow. Moreover, serum levels of ferritin and lactate dehydrogenase were elevated, hypercytokinemia was present, and soluble interleukin-2 receptor levels were increased up to 18.6-fold. The diagnosis of lysinuric protein intolerance should therefore be considered in any patient presenting with hemophagocytic lymphohistiocytosis. (J Pediatr 1999;134:236-9)

Lysinuric protein intolerance masquerading as celiac disease: A case report

A 5½-year-old boy presented with delayed growth, chronic diarrhea, and hypoproteinemia. Clinical presentation, initial laboratory data, and evaluation of an intestinal biopsy specimen suggested a diagnosis of celiac disease. Symptoms did not resolve on a gluten-free diet. The development of hyperammonemia prompted further studies that led to the diagnosis of lysinuric protein intolerance. Lysinuric protein intolerance, although a rare disorder, should be included in the differential diagnosis of conditions associated with intestinal villous atrophy. ( J Pediatr 1998;132:153-5)

Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset

Hyperammonemia and encephalopathy developed in an 11-year-old girl with chronic interstitial lung disease and cholesterol casts in her lung biopsy specimen. She had decreased plasma levels of ornithine, lysine, and arginine and excessive urinary excretion of lysine and arginine, consistent with the diagnosis of lysinuric protein intolerance. Analysis of plasma and urinary amino acids should be considered in the diagnostic evaluation of patients with interstitial lung disease of uncertain origin.

A difficult diagnosis of lysinuric protein intolerance: association with glucose‐6‐phosphate dehydrogenase deficiency

A difficult diagnosis of lysinuric protein intolerance: association with glucose‐6‐phosphate dehydrogenase deficiency

Advances in the use of computerized gas chromatography—mass spectrometry and high-performance liquid chromatography with rapid scanning detection for clinical diagnosis

A multi-component analytical system designed for the diagnosis of metabolic disorders is described. The urinary components are separated by a variety of chromatographic techniques, including automated amino acid analysis, high-performance liquid chromatography with diode-array detection and gas chromatography—mass spectrometry with a computerized mass spectral library search for identification of organic acids. The complete system can be used to diagnose over 100 different metabolic diseases. The usefulness of the chromatographic system is exemplified by the pre- and postnatal diagnosis of glutaric aciduria type I, the diagnosis of lysinuric protein intolerance and of alkaptonuria. Drugs and diet may cause interfering metabolites, as exemplified by glycofurol, used as a solvent for intnravenous drugs, and saccharin. It is predicted that chromatography and mas spectometry will continue to be important diagnostic tools for many years ahead.