Abstract
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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Communicated by: Carlo Dionisi-Vici, MD
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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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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. https://doi.org/10.1007/8904_2015_509
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DOI: https://doi.org/10.1007/8904_2015_509
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