Hemophagocytic lymphohistiocytosis and pulmonary alveolar proteinosis in a 13-month-old boy with lysinuric protein intolerance

Stanley, Robert F.; Licata, Michael; Sinha, Arpan A.; Wang, Yanhua

doi:10.5430/crcp.v4n3p19

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Renal function surveillance should be emphasized [14]. As well, hemophagocytic lymphohistiocytosis, characterized by hepatosplenomegaly, fever and cytopenia, can develop secondary to LPI, causing excessive activation of the immune system and secretion of pro-inflammatory cytokines [20].…”

Section: Discussionmentioning

confidence: 99%

Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis

Alqarajeh

Omorodion

Bosfield

et al. 2020

TRD

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BACKGROUND: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder characterized by deficient membrane transport of cationic amino acids. It is caused by pathogenic variants in SLC7A7, resulting in impairment of intestinal import and renal proximal tubule loss of the affected amino acids. LPI typically presents with gastrointestinal symptoms, such as vomiting, diarrhea, and failure to thrive. CASE REPORT: A 4-year-old African-American boy presented with multiple respiratory tract infections, weight loss in the setting of chronic diarrhea and worsening abdominal distention, and multiple episodes of rectal prolapse. Development was unaffected. Laboratory examination demonstrated mild anemia, hypokalemia and hypoalbuminemia, transaminitis, and normal ammonia. Initial urine amino acid analysis did not show major elevations of lysine and ornithine, often lower than expected in the setting of malnutrition. Upon initiation of total parenteral nutrition (TPN), his urine amino acids showed a characteristic profile of dibasic aminoaciduria. CONCLUSIONS: Failure to thrive, chronic diarrhea, and hepatomegaly should raise suspicion for LPI. Urine amino acids can be normal in this condition in the setting of malnutrition, a common complication of the disease. Additionally, it has been previously shown that the plasma arginine and ornithine concentration is higher in LPI subjects.

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Section: Discussionmentioning

confidence: 99%

Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis

Alqarajeh

Omorodion

Bosfield

et al. 2020

TRD

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“…The heteromeric y + LAT1 transporter, composed of a light subunit (encoded by SLC7A7 ) and a heavy subunit (encoded by SLC3A2 ), catalyzes the transmembrane efflux of arginine, lysine and ornithine in certain epithelial and non-epithelial cell types ( Broer, 2008 ; Broer and Gauthier-Coles, 2022 ; Palacin et al, 2004 ). LPI is a severe multi-system disorder characterized by growth failure ( Awrich et al, 1975 ; Goto et al, 1984 ; Carpenter et al, 1985 ; Nagata et al, 1987 ; Takada et al, 1987 ; Parini et al, 1991 ; Svedstrom et al, 1993 ; Parenti et al, 1995 ; Parsons et al, 1996 ; Kamoda et al, 1998 ; Korman et al, 2002 ; Moosa et al, 2005 ; Esposito et al, 2006 ; Gomez et al, 2006 ; Ogier de Baulny et al, 2012 ; Ko et al, 2012 ; Guzel-Ozanturk et al, 2013 ; Posey et al, 2014 ; Evelina et al, 2015 ; Bijarnia-Mahay et al, 2016 ; Deogaonkar and Shah, 2016 ; Noguchi et al, 2016 ; Mauhin et al, 2017 ; Stanley et al, 2017 ; Zhang and Cao, 2017 ; Olgac et al, 2020 ; Kang et al, 2019 ; Aljishi et al, 2020 ; Contreras et al, 2021 ; Andrews et al, 2021 ; Al-Qattan et al, 2021 ; Hashmi and Ahmed, 2022 ; Lee et al, 2022 ; Alqarajeh et al, 2020 ; Nicolas et al, 2016 ), short stature ( Awrich et al, 1975 ; Goto et al, 1984 ; Carpenter et al, 1985 ; Nagata et al, 1987 ; Takada et al, 1987 ; Parini et al, 1991 ; Parenti et al, 1995 ; Parsons et al, 1996 ; Kamoda et al, 1998 …”

Section: Introductionmentioning

confidence: 99%

Delayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance

Stroup,

Li,

et al. 2023

Disease Models &Amp; Mechanisms

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SLC7A7 deficiency, or lysinuric protein intolerance (LPI), causes loss of function of the y+LAT1 transporter critical for efflux of arginine, lysine and ornithine in certain cells. LPI is characterized by urea cycle dysfunction, renal disease, immune dysregulation, growth failure, delayed bone age, and osteoporosis. We previously reported that Slc7a7 knockout mice (C57BL/6 x 129/SvEv F2) recapitulate LPI phenotypes, including growth failure. Our main objective was to characterize the skeletal phenotype in these mice. Compared to wild type littermates, juvenile Slc7a7 knockout mice demonstrated 70% lower body weights, 87% lower plasma IGF-1 concentrations, and delayed skeletal development. Because poor survival prevents evaluation of mature knockout mice, we generated a conditional Slc7a7 deletion in mature osteoblasts or mesenchymal cells of the osteo-chondroprogenitor lineage, butno differences in bone architecture were observed. Overall, global Slc7a7 deficiency caused growth failure with low plasma IGF-1 concentrations and delayed skeletal development, but Slc7a7 deficiency in the osteoblastic lineage was not a major contributor to these phenotypes. Future studies utilizing additional tissue-specific Slc7a7 knockout models may help dissect cell autonomous and non-cell autonomous mechanisms underlying phenotypes in LPI.

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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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Hemophagocytic lymphohistiocytosis and pulmonary alveolar proteinosis in a 13-month-old boy with lysinuric protein intolerance

Cited by 3 publications

References 21 publications

Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis

Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis

Delayed skeletal development and IGF-1 deficiency in a mouse model of lysinuric protein intolerance

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

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