Lysinuric Protein Intolerance and Hartnup Disease

2016 ◽  
Author(s):  
Gianfranco Sebastio ◽  
Manuel Schiff ◽  
Hélène Ogier de Baulny
Keyword(s):  
Amino Acid ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Basolateral Membrane ◽  
Neurological Involvement ◽  
Lysinuric Protein Intolerance ◽  
Cationic Amino Acid ◽  
Transporter Family ◽  
Lysinuric Protein ◽  
Protein Intolerance

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. Symptoms usually begin after weaning with refusal of feeding, vomiting, and consequent failure to thrive. Hepatosplenomegaly, hematological anomalies, and neurological involvement including hyperammonemic coma will progressively appear. Lung involvement (specifically pulmonary alveolar proteinosis), chronic renal disease that may lead to end stage renal disease, and hemophagocytic lymphohistiocytosis with macrophage activation all represent complications of LPI that may appear at any time from childhood to adulthood. The great variability of the clinical presentation frequently causes misdiagnosis or delayed diagnosis. The basic therapy of LPI consist of a low-protein diet, low-dose citrulline supplementation, nitrogen-scavenging compounds to prevent hyperammonemia, lysine, and carnitine supplements.

scholarly journals Lysinuric protein intolerance: an overlooked diagnosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Asburce Olgac ◽  
Idil Yenicesu ◽  
Rıza Köksal Ozgul ◽  
Gürsel Biberoğlu ◽  
Leyla Tümer
Keyword(s):  
Amino Acid ◽  
Complete Blood Count ◽  
Clinical Symptoms ◽  
Basolateral Membrane ◽  
Genetic Defect ◽  
Good Condition ◽  
Homozygous Mutation ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Protein Intolerance

Abstract Background Lysinuric protein intolerance (LPI) is an autosomal recessively inherited inborn error of metabolism (IEM) caused by the defect in the dibasic cationic amino acid transporter found on the basolateral membrane of the lung, small intestine, and kidney due to mutations in the SLC7A7 gene, which encodes the y+LAT1 protein. LPI may present as an acute hyperammonemic episode or as chronic symptoms. Major clinical symptoms are feeding problems, vomiting and diarrhea, failure to thrive, hepatosplenomegaly, and cytopenia. We present a delayed diagnosis of symptomatic LPI with a homozygous mutation in the SLC7A7 gene. Case presentation A 15-year-old girl was referred to our clinic due to growth retardation and diarrhea. Physical examination showed short stature, retarded puberty, and hepatosplenomegaly. Laboratory tests showed normal complete blood count and biochemical analyses except elevated aspartate aminotransferase, triglyceride, total cholesterol, and ferritin. Peripheral blood smear and hemoglobin electrophoresis were within normal limits. Bone marrow analysis showed hemophagocytic cells. Postprandial ammonium level was found elevated. Low lysine, arginine, and ornithine and elevated glycine and alanine in plasma amino acid analysis and high amount of lysine and slightly elevated arginine and ornithine excretion in urine were detected. Molecular genetic analysis of the SLC7A7 gene showed a previously reported homozygous mutation. Low protein diet, sodium benzoate, l-carnitine, low-dose l-citrulline, and calcium replacement were initiated. The patient is now in good condition still being followed up in our department. Conclusions LPI is a metabolic disorder with multi-systemic involvement that may have severe consequences if left untreated. Initiation of early treatment is essential for the prevention of severe chronic complications. Also, confirmation of the genetic defect may provide the parents to have healthy offsprings in the future with the help of genetic counselling and preimplantation genetics.

scholarly journals Inducible Slc7a7 Knockout Mouse Model Recapitulates Lysinuric Protein Intolerance Disease

2019 ◽  
Vol 20 (21) ◽  
pp. 5294 ◽  
Author(s):  
Bodoy ◽  
Sotillo ◽  
Espino-Guarch ◽  
Sperandeo ◽  
Ormazabal ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Failure To Thrive ◽  
Neurological Impairment ◽  
Lysinuric Protein Intolerance ◽  
Metabolic Derangement ◽  
Knockout Mouse Model ◽  
Cationic Amino Acid ◽  
Promising Tool ◽  
Lysinuric Protein ◽  
Protein Intolerance

Lysinuric protein intolerance (LPI) is a rare autosomal disease caused by defective cationic amino acid (CAA) transport due to mutations in SLC7A7, which encodes for the y+LAT1 transporter. LPI patients suffer from a wide variety of symptoms, which range from failure to thrive, hyperammonemia, and nephropathy to pulmonar alveolar proteinosis (PAP), a potentially life-threatening complication. Hyperammonemia is currently prevented by citrulline supplementation. However, the full impact of this treatment is not completely understood. In contrast, there is no defined therapy for the multiple reported complications of LPI, including PAP, for which bronchoalveolar lavages do not prevent progression of the disease. The lack of a viable LPI model prompted us to generate a tamoxifen-inducible Slc7a7 knockout mouse (Slc7a7−/−). The Slc7a7−/− model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of CAA, hypoargininemia and hyperammonemia. Interestingly, the Slc7a7−/− mice also develops PAP and neurological impairment. We observed that citrulline treatment improves the metabolic derangement and survival. On the basis of our findings, the Slc7a7−/− model emerges as a promising tool to further study the complexity of LPI, including its immune-like complications, and to design evidence-based therapies to halt its progression.

scholarly journals Waste Nitrogen Excretion Via Amino Acid Acylation: Benzoate and Phenylacetate in Lysinuric Protein Intolerance

1986 ◽  
Vol 20 (11) ◽  
pp. 1117-1121 ◽  
Author(s):  
Olli Simell ◽  
Ilkka Sipilä ◽  
Jukka Rajantie ◽  
David L Valle ◽  
Saul W Brusilow
Keyword(s):  
Amino Acid ◽  
Nitrogen Excretion ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Protein Intolerance

Apical Transporters for Neutral Amino Acids: Physiology and Pathophysiology

Physiology ◽  
2008 ◽  
Vol 23 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Stefan Bröer
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Molecular Identification ◽  
Molecular Basis ◽  
Amino Acid Transporters ◽  
Lysinuric Protein Intolerance ◽  
Inherited Disorders ◽  
Lysinuric Protein ◽  
Hartnup Disorder ◽  
Protein Intolerance

Absorption of amino acids in kidney and intestine involves a variety of transporters for different groups of amino acids. This is illustrated by inherited disorders of amino acid absorption, such as Hartnup disorder, cystinuria, iminoglycinuria, dicarboxylic aminoaciduria, and lysinuric protein intolerance, affecting separate groups of amino acids. Recent advances in the molecular identification of apical neutral amino acid transporters has shed a light on the molecular basis of Hartnup disorder and iminoglycinuria.

scholarly journals Interactions of y+LAT1 and 4F2hc in the y+l amino acid transporter complex: consequences of lysinuric protein intolerance-causing mutations

2013 ◽  
Vol 32 (04) ◽  
pp. 479-488 ◽  
Author(s):  
Minna Toivonen, ◽  
Maaria Tringham ◽  
Johanna Kurko ◽  
Perttu Terho ◽  
Olli Simell ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transporter ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Acid Transporter ◽  
Protein Intolerance

Lysinuric protein intolerance. Urinary amino acid excretion at 2 and 9 days of age

1994 ◽  
Vol 17 (2) ◽  
pp. 252-253 ◽  
Author(s):  
M. Candito ◽  
C. Vianey-Saban ◽  
J. P. Ferraci ◽  
B. B�bin ◽  
J. P. Chazalette ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Excretion ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Urinary Amino ◽  
Protein Intolerance
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