title: Renal Involvement in a French Paediatric Cohort of Patients with Lysinuric Protein Intolerance.
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.
authors.affiliation: Department of Paediatrics, Nephrology Paediatric Unit, CHU Reims, France. cnicolas@chu-reims.fr.
authors.forename: C
authors.initials: C
authors.lastname: Nicolas
authors.affiliation: Department of Neonatalogy, Metabolic Unit, CHU Reims, France.
authors.forename: N
authors.initials: N
authors.lastname: Bednarek
authors.affiliation: Departments of Nephrology and Pathology, CHU de Reims, France.
authors.forename: V
authors.initials: V
authors.lastname: Vuiblet
authors.affiliation: Department of Paediatric Nephrology, APHP Necker Enfants-Malades Hospital, INSERM U1163, Imagine Institute, Paris Descartes University, Sorbonne Paris Cité University, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Boyer
authors.affiliation: Department of Metabolic Diseases, APHP Necker Enfants-Malades Hospital, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Brassier
authors.affiliation: Department of Metabolic Diseases, APHP Necker Enfants-Malades Hospital, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: De Lonlay
authors.affiliation: Department of Pathology, APHP Necker Enfants-Malades Hospital, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Galmiche
authors.affiliation: Department of Paediatric Nephrology, APHP Necker Enfants-Malades Hospital, INSERM U1163, Imagine Institute, Paris Descartes University, Sorbonne Paris Cité University, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Krug
authors.affiliation: Department of Paediatric Nephrology, APHP Robert Debré Hospital, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Baudouin
authors.affiliation: Reference Center of Inborn Errors of Metabolism, APHP Robert Debré Hospital, INSERM U1141, Paris-Diderot University, Sorbonne Paris Cité University, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Pichard
authors.affiliation: Reference Center of Inborn Errors of Metabolism, APHP Robert Debré Hospital, INSERM U1141, Paris-Diderot University, Sorbonne Paris Cité University, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Schiff
authors.affiliation: Department of Paediatrics, Nephrology Paediatric Unit, CHU Reims, France.
authors.forename: C
authors.initials: C
authors.lastname: Pietrement
keywords: Children; Glomerulonephritis; Lysinuric protein intolerance; Nephrocalcinosis