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

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JIMD Reports, Volume 29


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.

Competing interests: None declared

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  • Aoki M, Fukao T, Fujita Y et al (2001) Lysinuric protein intolerance in siblings: complication of systemic lupus erythematosus in the elder sister. Eur J Pediatr 160(8):522–523

    Article  CAS  PubMed  Google Scholar 

  • Benninga M, Lilien M, De Koning T et al (2007) Renal Fanconi syndrome with ultrastructural defects in lysinuric protein intolerance. J Inherit Metab Dis 30(3):402–403

    Article  CAS  PubMed  Google Scholar 

  • Camargo S, Bockenhauer D, Kleta R (2008) Aminoacidurias: clinical and molecular aspects. Kidney Int 73(8):918–925

    Article  CAS  PubMed  Google Scholar 

  • Di Rocco M, Buoncompagni A, Gatton M et al (1998) Complications of lysinuric protein intolerance must be treated with immunosuppressive drugs. J Inher Metab Dis 21(6):675–676

    Article  PubMed  Google Scholar 

  • Dionisi-Vici D, De Felice L, el Hachem M et al (1998) Intravenous immune globulin in lysinuric protein intolerance. J Inherit Metab Dis 21(2):95–102

    Article  CAS  PubMed  Google Scholar 

  • Kamoda T, Nagai Y, Shigeta M (1998) Lysinuric protein intolerance and systemic lupus erythematosus. Eur J Pediatr 157(2):130–131

    Article  CAS  PubMed  Google Scholar 

  • Mannucci L, Emma F, Markert M et al (2005) Increased NO production in lysinuric protein intolerance. J Inherit Metab Dis 28(2):123–129

    Article  CAS  PubMed  Google Scholar 

  • Nagasaka H, Tsukahara H, Yorifuji T et al (2009) Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects. Metab Clin Exp 58(3):278–282

    Article  CAS  PubMed  Google Scholar 

  • Ogier de Baulny H, Schiff M, Dionisi-Vici C (2012) Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder. Mol Genet Metab 106(1):12–17

    Article  CAS  PubMed  Google Scholar 

  • Palacin M, Bertran J, Chillaron J (2004) Lysinuric protein intolerance: mechanisms of pathophysiology. Mol Genet Metab 81(Suppl 1):S27–S37

    Google Scholar 

  • Parenti G, Sebastio G, Strisciuglio P (1995) Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course. J Pediatr 126(2):246–251

    Article  CAS  PubMed  Google Scholar 

  • Parto K, Kallajoki M, Aho H et al (1994) Pulmonary alveolar proteinosis and glomerulonephritis in lysinuric protein intolerance: case reports and autopsy findings of four pediatric patients. Hum pathol 25(4):400–407

    Article  CAS  PubMed  Google Scholar 

  • Sebastio G, Sperandeo MP, Andria G (2011) Lysinuric protein intolerance: reviewing concepts on a multisystem disease. Am J Med Genet C Semin Med Genet 157C(1):54–62

    Article  PubMed  Google Scholar 

  • Sperandeo MP, Paladino S, Maiuri L et al (2005) A y(+)LAT-1 mutant protein interferes with y(+) LAT-2 activity: implications for the molecular pathogenesis of lysinuric protein intolerance. Eur J Hum Genet 13(5):628–634

    Article  CAS  PubMed  Google Scholar 

  • Tanner L, Näntö-Salonen K, Niinikoski H et al (2007) Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance. J Pediatr 150(6):631–634

    Article  PubMed  Google Scholar 

  • Thelle K, Christensen E, Vorum H (2006) Characterization of proteinuria and tubular protein uptake in a new model of oral L-Lysine administration in rats. Kidney Int 69(8):1333–1340

    Article  CAS  PubMed  Google Scholar 

  • Torrents D, Mykkänen J, Pineda M et al (1999) Identification of SLC7A7, encoding y+LAT-1 as the lysinuric protein intolerance gene. Nat Genet 21(3):293–296

    Article  CAS  PubMed  Google Scholar 

  • Verzola D, Fama A, Villaggio B et al (2012) Lysine triggers apoptosis through a NADPH oxidase-dependent mechanism in human renal tubular cells. J Inherit Metab Dis 35(6):1011–1019

    Article  CAS  PubMed  Google Scholar 

  • Yoshida Y, Machigashira K, Suehara M et al (1995) Immunological abnormality in patients with lysinuric protein intolerance. J Neurol Sci 134(1-2):178–182

    Article  CAS  PubMed  Google Scholar 

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Correspondence to C. Nicolas .

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Communicated by: Carlo Dionisi-Vici, MD


Take-Home Message

Kidney involvement can complicate lysinuric protein intolerance, and it is therefore essential to monitor patients for the appearance of kidney diseases such as tubulopathy or glomerulopathy.

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Conflict of Interest

Camille Nicolas, Nathalie Bednarek, Vincent Vuiblet, Olivia Boyer, Anais Brassier, Pascale De Lonlay, Louise Galmiche, Pauline Krug, Véronique Baudouin, Samia Pichard, Manuel Schiff, Christine Pietrement declare that they have no conflict of interest.

All authors have nothing to declare.

The authors declare that the content of the article has not been influenced by the sponsors.

This article does not contain any studies with animal performed by the any of the authors.

Patient care and study conduct complied with good clinical practice and the Declaration of Helsinki Principles.

Camille Nicolas wrote the paper and gathered patients’ data. Vincent Vuiblet and Louise Galmiche interpreted the biopsy pictures, and all authors contributed to the interpretation and final manuscript preparation.

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Nicolas, C. et al. (2015). Renal Involvement in a French Paediatric Cohort of Patients with Lysinuric Protein Intolerance. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 29. JIMD Reports, vol 29. Springer, Berlin, Heidelberg.

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