Intravenous immune globulin in lysinuric protein intolerance

Dionisi‐Vici, Carlo; Felice, L. De; Hachem, Maya El; Bottero, Sergio; Rizzo, Cristiano; Paoloni, A; Goffredo, Bianca Maria; Sabetta, G.; Caniglia, Maurizio

doi:10.1023/a:1005383307100

Cited by 23 publications

(3 citation statements)

References 10 publications

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“…Five asymptomatic patients were described, however, one of them had postprandial hyperammonemia after a protein loading test, while another died suddenly of unknown causes. Five patients presented simultaneously with SLE and LPI, and three patients had lupus-like symptoms that were ultimately attributed to LPI ( 53 – 55 ). LPI was also reported to mimic other immune dysregulatory diseases including HLH ( 14 , 22 ) and celiac disease ( 16 ), leading to initial misdiagnoses.…”

Section: Resultsmentioning

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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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: Resultsmentioning

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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“…LPI treatment was to reduce the risk of hyperammonemia, and to provide relatively sufficient proteins and essential amino acids to maintain natural growth, as well as treatment for related complications. 6,7 The main measures to reduce the risk of were a low-protein diet and citrulline replacement therapy. When blood ammonia levels were within the normal range, protein intake could be appropriately increased to promote growth.…”

Section: Discussionmentioning

confidence: 99%

Lysinuric protein intolerance associated systemic lupus erythematosus with new mutations in the SLC7A7 gene

Chen

liu

Wang

et al. 2022

Preprint

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Background: Lysinuric protein tolerance (LPI) is a rare autosomal, recessive, metabolic disease caused by mutations in the SLC7A7 gene. It was first reported in the Finnish population in 1965, and involved multiple organ systems like the digestive, blood, respiratory, nervous, urinary and other systems, due to a defect in the transport of the dialkylamino acid plasma membrane. Case presentation: A girl with severe malnutrition, underdevelopment and a long-term history of hepatosplenomegaly, presented with recurrent fever, cough and shortness of breath. Computer tomography (CT) revealed that she had a considerable lung infection, and the results of laboratory tests showed that she had moderate anemia. The maximum value of type B natriuretic peptide (BNP) was 6076 ng/L (0-300). In this course, the blood ammonia was 85.5 μmol/L (11-40), the serum ferritin was 3827 ng/mL (10-120), the complement 3 was 237 mg/L (790-1520), complement 4 was 53.1 mg/L (100-400), the titre of anti-nuclear antibody (ANA) was 1:320 and the anti-dsDNA antibody was positive. The patient died of severe pneumonia at 5 years old. A genetic test indicated that the patient’s SLC7A7 gene had a compound heterozygous mutation, including c.724T>C chr14-23248048 p.W242R and c.719C>T chr14-23248053 p.S240L, inherited from the patient’s father and mother, respectively. Conclusions: The patient was diagnosed with LPI with systemic lupus erythematosus (SLE), and severe pneumonia, and her SLC7A7 gene had a compound heterozygous mutation.

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“…Macrophages are considered to be key for the immune and hematological abnormalities of LPI. For instance, erythroblastophagocytosis (the process of erythroblast phagocytosis) has been reported in some patients with LPI (Dionisi-Vici et al 1998; Parenti et al 1995). Hematological complications can also include microcytic and/or hypochronic anemia, hemophagocytic lymphohistiocytosis and loss of megakaryocyte populations (Duval et al 1999; Korman et al 2002; Noguchi and Takahashi 2019).…”

Section: Introductionmentioning

confidence: 99%

DefectiveSlc7a7transport reduces erythropoietin compromising erythropoiesis and iron homeostasis

Sotillo

Giroud-Gerbetant

Couso

et al. 2021

Preprint

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Slc7a7 encodes for y+LAT1, a transporter of cationic amino acid across the basolateral membrane of epithelial cells. Mutations in SLC7A7 gene give rise to Lysinuric Protein Intolerance (LPI), a rare autosomal recessive disease with wide variability of complications. Intriguingly, y+LAT1 is also involved in arginine transport in non polarized cells such as macrophages. Here we report that complete inducible Slc7a7 ablation in mouse compromises systemic arginine availability that alters proper erythropoiesis and that dysfunctional RBC generation leads to increased erythrophagocytosis, iron overload and an altered iron metabolism by macrophages. Herein, uncovering a novel mechanism that links amino acid metabolism to erythropoiesis and iron metabolism. Mechanistically, the iron exporter ferroportin-1 expression was compromised by increased plasma hepcidin causing macrophage iron accumulation. Strikingly, lysozyme M-cell-specific knockout mice failed to reproduce the total knockout alterations, while bone marrow transplantation experiments resulted in the resolution of macrophage iron overload but could not overcome erythropoietic defect. This study establishes a new crucial link between systemic arginine availability in erythropoiesis and iron homeostasis.

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Intravenous immune globulin in lysinuric protein intolerance

Cited by 23 publications

References 10 publications

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

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

Lysinuric protein intolerance associated systemic lupus erythematosus with new mutations in the SLC7A7 gene

DefectiveSlc7a7transport reduces erythropoietin compromising erythropoiesis and iron homeostasis

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