Overview of symptoms and treatment for lysinuric protein intolerance

Noguchi, Atsuko; Takahashi, Tsutomu

doi:10.1038/s10038-019-0620-6

Cited by 34 publications

(22 citation statements)

References 75 publications

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“…CAA transport, especially of arginine, in non-polarized (epithelial) cells such as macrophages and lymphocytes is mainly carried out by y+LAT1 which decreased in patients with LPI ( 74 , 75 ). Thus, it has been hypothesized that impaired arginine efflux results in increased intracellular arginine concentrations and augments nitric oxide (NO) production ( 12 ). Arginine is the exclusive substrate of inducible nitric oxide synthase (iNOS) which catalyzes the conversion of L-arginine to L-citrulline and NO.…”

Section: Discussionmentioning

confidence: 99%

“…SLC7A7 maps to chromosome 14q11.2 ( 11 ), and encodes amino acid transporter 1 (y+LAT1). y+LAT is the light subunit isoform of the y+L system; it associates with the heavy subunit 4F2hc to form a heterodimeric transporter responsible for the transport of CAA, allowing the efflux of CAA from polar and non-polar cells ( 12 ). The molecular basis of LPI is limited to SLC7A7 variants, as pathologic loss of SLC3A2 , which encodes 4F2hc, has not been described in humans ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Immune Dysregulation Mimicking Systemic Lupus Erythematosus in a Patient With Lysinuric Protein Intolerance: Case Report and Review of the Literature

et al. 2021

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Lysinuric protein intolerance (LPI) is an inborn error of metabolism caused by defective transport of cationic amino acids in epithelial cells of intestines, kidneys and other tissues as well as non-epithelial cells including macrophages. LPI is caused by biallelic, pathogenic variants in SLC7A7. The clinical phenotype of LPI includes failure to thrive and multi-system disease including hematologic, neurologic, pulmonary and renal manifestations. Individual presentations are extremely variable, often leading to misdiagnosis or delayed diagnosis. Here we describe a patient that clinically presented with immune dysregulation in the setting of early-onset systemic lupus erythematosus (SLE), including renal involvement, in whom an LPI diagnosis was suspected post-mortem based on exome sequencing analysis. A review of the literature was performed to provide an overview of the clinical spectrum and immune mechanisms involved in this disease. The precise mechanism by which ineffective amino acid transport triggers systemic inflammatory features is not yet understood. However, LPI should be considered in the differential diagnosis of early-onset SLE, particularly in the absence of response to immunosuppressive therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune Dysregulation Mimicking Systemic Lupus Erythematosus in a Patient With Lysinuric Protein Intolerance: Case Report and Review of the Literature

et al. 2021

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“…At around one year of age, patients commonly develop a strong aversion to high-protein foods with failure to thrive. In addition, the spleen and liver may be moderately enlarged [137]. Recurrent fractures occur frequently and rates of high, severe osteoporosis are observed from childhood to adulthood [138][139][140].…”

Section: Lysinuric Protein Intolerance (Omim #222700)mentioning

confidence: 99%

“…In many cases, hyperammonemia may be triggered by starvation, infection, and stress. Some patients only show transient mild hyperammonemia after meals [137,141]. Some patients may present with mild normochromic or hypochromic anemia, leukopenia, and thrombocytopenia.…”

Section: Lysinuric Protein Intolerance (Omim #222700)mentioning

confidence: 99%

“…Disturbed proximal tubular function with mild proteinuria, tubular acidosis, and microhematuria may begin in childhood and often progress to glomerular dysfunction and end-stage renal failure [143][144][145]. Frequent complications include bone marrow involvement with hemophagocytic lymphohistiocytosis and interstitial pulmonary disease with alveolar proteinosis [137,146]. A few children and adults have died following a very uniform course of progressive multiple organ failure with interstitial lung involvement, progressive glomerulonephritis, and severe bleeding diathesis [147].…”

Section: Lysinuric Protein Intolerance (Omim #222700)mentioning

confidence: 99%

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Amino Acid Transport Defects in Human Inherited Metabolic Disorders

Yahyaoui

Pérez‐Frías

2019

IJMS

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Amino acid transporters play very important roles in nutrient uptake, neurotransmitter recycling, protein synthesis, gene expression, cell redox balance, cell signaling, and regulation of cell volume. With regard to transporters that are closely connected to metabolism, amino acid transporter-associated diseases are linked to metabolic disorders, particularly when they involve different organs, cell types, or cell compartments. To date, 65 different human solute carrier (SLC) families and more than 400 transporter genes have been identified, including 11 that are known to include amino acid transporters. This review intends to summarize and update all the conditions in which a strong association has been found between an amino acid transporter and an inherited metabolic disorder. Many of these inherited disorders have been identified in recent years. In this work, the physiological functions of amino acid transporters will be described by the inherited diseases that arise from transporter impairment. The pathogenesis, clinical phenotype, laboratory findings, diagnosis, genetics, and treatment of these disorders are also briefly described. Appropriate clinical and diagnostic characterization of the underlying molecular defect may give patients the opportunity to avail themselves of appropriate therapeutic options in the future.

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