[Kidney injury in children and adolescents with leptospirosis in France]. / Atteinte rénale chez les enfants infectés par la leptospirose en France.

INTRODUCTION: Leptospirosis is an anthropozoonosis with polymorphic clinical symptoms and a high variability of severity, ranging from flu-like syndrome to severe acute kidney injury. This disease is highly incident in tropical regions but there is a trend towards increasing incidence in metropolitan France and in Reunion Island. The objective of this study was to describe the epidemiological, clinical, laboratory and therapeutic characteristics of the pediatric leptospirosis in metropolitan France and in Reunion Island. PATIENTS AND METHODS: We performed a retrospective analysis of leptospirosis cases hospitalized in University hospitals where members of the Paediatric Nephrology Society work in France between January 2008 and December 2020, 6 centers reported leptospirosis cases, one center had one patient in consultation but lack of available data and 10 centers did not find any case. RESULTS: A total of 21 cases were reported (mean age 13.4±3.4years), mostly boys (ratio 6:1). Out of 21 patients, 95% had fever, 71% were presenting with myalgia, 81% with thrombocytopenia, and 76% with gastrointestinal symptoms. Regarding kidney impairment, 18 patients (86%) had acute kidney injury, including 4 (19%) with oligoanuria, but none of them required acute dialysis. About 30% of patients had biological signs of tubulopathy including hypophosphatemia, hypokalemia, or tubular proteinuria. No death due to the disease occurred. The therapeutic management followed the current guidelines with the use of antibiotic therapy by amoxicillin or 3rd generation cephalosporins with symptomatic treatment. When there was biological control after exit, creatinine decreased. DISCUSSION: In this multicenter retrospective study, we report 21 children with leptospirosis with a significant proportion of acute kidney injury, the outcome was favorable. Children do not seem to be at high risk of chronic kidney disease progression but nephrology follow-up has not been systematically carried out. Compared to studies performed in adults, the prognosis was better and hepatic impairment was rare. Compared to other pediatric studies, conjunctivitis was not a common symptom but kidney injury and survival appeared to be similar. Children were presenting with anicteric renal presentation. The casebook wasn't exhaustive and didn't include the other overseas territories, which account for the highest proportion of leptospirosis infection. CONCLUSION: Leptospirosis is an infection which may lead to multivisceral failure with kidney involvement conditioning the outcome. Despite a better prognosis in children, it remains important to quickly diagnose this infection in order to start appropriate antibiotic therapy and perform a kidney function monitoring.

When a maternal heterozygous mutation of the CYP24A1 gene leads to infantile hypercalcemia through a maternal uniparental disomy of chromosome 20.

BACKGROUND: Infantile hypercalcemia is an autosomal recessive disorder caused either by mutations in the CYP24A1 gene (20q13.2) or in the SLC34A1 gene (5q35.3). This disease is characterized by hypercalcemia, hypercalciuria and nephrocalcinosis in paediatric patients. Maternal uniparental disomy of chromosome 20 [UPD(20)mat], resulting in aberrant expression of imprinted transcripts at the GNAS locus, is a poorly characterized condition. UPD(20)mat patients manifest a phenotype similar to that of Silver-Russell syndrome and small for gestational age-short stature. CASE PRESENTATION: We report here the genetic and clinical characterization of a male child with a phenotype of infantile hypercalcemia, postnatal growth retardation, and minor dysmorphic features. Genetic analysis using a next generation sequencing panel revealed a homozygous pathogenic variant of CYP24A1. The absence of the variant in the father led to microsatellite segregation analysis, suggestive of UPD. SNP-array revealed a large terminal copy neutral loss of heterozygosity leading to CYP24A1 homozygosity. SNP-array data of parent-child trio confirmed a UPD(20)mat responsible for both infantile hypercalcemia and Silver-Russell syndrome-like traits. CONCLUSION: This is the first report of uniparental disomy of chromosome 20 revealed by infantile hypercalcemia related to CYP24A1 biallelic homozygous variants, underlying the importance of controlling allelic segregation in cases of homozygosity.