Abstract Objective To describe the clinical presentation of 10 patients with type 3 Gaucher disease and the clinical evolution of nine of them following specific therapy regimes. Methods: The ...follow-up of these 10 patients was between 2 and 15 years. The clinical history was provided by each patient’s general practitioner and a final clinical evaluation was made by two different physicians including a neurologist. One patient received no treatment, eight received enzyme replacement therapy (ERT) and one received ERT combined with substrate reduction therapy (SRT, miglustat). Results: The clinical presentations were heterogeneous and most phenotypes reported for type 3 Gaucher disease were represented. The neurological involvement stabilized or improved in six patients under ERT with a follow-up of 2–15 years. Four of them showed isolated oculomotor signs only that improved or remained unchanged during the follow-up. Of two patients with progressive myoclonic epilepsy, the outcome was clearly unfavorable in one receiving ERT and disputable for the other receiving ERT + SRT. An unfavorable neurological outcome was observed in another patient in whom the ERT dose had been reduced before clinical decline. Conclusion: The stabilization of the clinical course in most patients is noteworthy. Though further evidence is needed from a larger series in order to draw any definite conclusions, our data suggest that ERT may be effective in preventing the evolution of neurological disturbances associated with type 3 Gaucher disease in some patients. However, the clinical course of the two patients with progressive myoclonic epilepsy was not influenced by ERT, as previously reported. In accordance with that reported in the literature, data from our series suggest that the outcome of patients undergoing ERT depends on the type of clinical involvement, treatment onset and dose. Genotype may also be an important factor, with p.L444P/p.L444P possibly indicating a better outcome.
Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but ...the optimal therapeutic strategy remains unknown.
To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C.
Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021.
IVIG and methylprednisolone vs IVIG alone.
The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1.
Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females 52%; median age, 8.6 years interquartile range, 4.7 to 12.1). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 95% CI, -0.48 to -0.08; odds ratio OR, 0.25 95% CI, 0.09 to 0.70; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 95% CI, -0.40 to -0.04; OR, 0.19 95% CI, 0.06 to 0.61; P = .004), hemodynamic support (absolute risk difference, -0.17 95% CI, -0.34 to -0.004; OR, 0.21 95% CI, 0.06 to 0.76), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 95% CI, -0.35 to -0.01; OR, 0.20 95% CI, 0.06 to 0.66), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 95% CI, -4.0 to -0.7).
Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.
Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ...ANCA-associated vasculitis (AAV).
We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years. Inclusion criteria were (i) granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to classification criteria of the European League Against Rheumatism/Paediatric Rheumatology European Society, and (ii) ANCA positivity. Patient and renal survival were analysed.
Among 66 children included, 80% were female, 42% had GPA and 58% MPA including renal-limited vasculitis, 67% were pANCA+ and 33% cANCA+. The mean incidence of reported cases increased to 0.45 per million children/year in the period 2006-10. Median age at diagnosis was 11.5 years, and median time to diagnosis was 1 month. Initial symptoms included fever and fatigue (79%), skin lesions (41%), arthritis (42%), pulmonary (45%) and renal involvement (88%). Clinical features were similar between GPA and MPA with the exception of upper airway impairment (28%) specific of GPA. Ninety percent of the patients achieved remission after induction treatment. After a median follow-up of 5.2 years, 4 patients (6%) died, corresponding to a mortality rate of 1.2 per 100 person-years, and 22 patients (34%) developed end-stage renal disease (ESRD). Renal survival was 74, 70 and 59% at 1, 5 and 10 years, respectively. In a multivariable Cox regression model, baseline glomerular filtration rate, ethnic origin, histopathological classification and era of treatment were associated with the occurrence of ESRD. Relapse-free survival was 57% at 5 years and 34% at 10 years of follow-up. Patient and renal outcome did not significantly differ between GPA and MPA.
Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time.
Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of ...Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vβ21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro
Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.
La leptospirose est une anthropozoonose dont le tableau clinique est polymorph e et de gravité variable, allant du syndrome pseudo-grippal à l’insuffisance rénale aiguë menaçante. Cette maladie à ...forte incidence dans les régions tropicales voit son incidence augmenter en France métropolitaine et à la Réunion. L’objectif de cette étude était d’identifier les caractéristiques épidémiologiques, cliniques, biologiques et thérapeutiques des formes pédiatriques de la leptospirose en France métropolitaine et à la Réunion.
Nous avons mené une étude de cohorte des cas de leptospirose pédiatriques hospitalisés dans les centres hospitaliers dans lesquels exercent des membres de la Société de néphrologie pédiatrique (SNP) entre janvier 2008 et décembre 2020. Parmi les centres répondeurs, six avaient eu des cas de leptospirose, un centre en avait eu un en consultation mais dont les données étaient insuffisantes, et dix n’en ont pas retrouvés.
Vingt-et-un cas ont été recensés dans six centres hospitalo-universitaires français (âge moyen 13,4±3,4ans), majoritairement des garçons (ratio 6:1). Parmi les 21 enfants, 95 % avaient de la fièvre, 71 % avaient des myalgies, 81 % avaient une thrombopénie et 76 % ont présenté des symptômes digestifs. Sur le plan rénal, 18 patients (86 %) présentaient une insuffisance rénale, dont 19 % avec oligoanurie, mais aucun n’a nécessité de dialyse. Environ 30 % des patients présentaient des signes biologiques de tubulopathie comprenant une hypophosphatémie, une hypokaliémie ou une protéinurie tubulaire. Il n’y a eu aucun décès. La prise en charge thérapeutique correspondait aux recommandations avec une antibiothérapie par amoxicilline ou céphalosporine de 3e génération associée à un traitement symptomatique de l’atteinte rénale. Lorsqu’il y a eu un contrôle biologique après la sortie, on observait une décroissance de la créatinine.
Dans cette étude rétrospective multicentrique, nous rapportons 21 cas d’infection par leptospirose, avec une proportion importante d’insuffisance rénale, dont l’évolution était favorable. L’évolution vers l’insuffisance rénale chronique ne semble pas être le cas chez les enfants, mais le suivi à distance n’a pas été systématiquement réalisé. Par rapport à des études menées chez les adultes, le pronostic global est meilleur et l’ictère est plus rare. Par rapport à d’autres études pédiatriques, la conjonctivite n’est pas un signe fréquent, mais les atteintes rénales et la survie sont similaires. On pourrait parler de formes rénales anictériques révélatrices. Le recueil de cas n’était pas exhaustif et ne comprenait pas les autres territoires d’outre-mer alors qu’ils regroupent la plus grande proportion d’infection par la leptospirose.
La leptospirose est une infection qui peut être responsable d’une défaillance multiviscérale avec une atteinte rénale conditionnant le pronostic vital. Malgré un meilleur pronostic chez l’enfant, il reste important de diagnostiquer rapidement cette infection afin de mettre en place l’antibiothérapie adaptée et un suivi néphrologique en cas d’atteinte rénale.
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.
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.
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.
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.
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.
Background
Pediatric ANCA vasculitis is a rare group of diseases with a scarcity of data in children. Annual incidence appeared to increase in the last several years, placing higher interest in the ...clinical and therapeutical outcomes of the disorder. Also, the growing use of rituximab questions the latest outcomes in these diseases. We therefore conducted a retrospective study to better understand the current characteristics, management, and the latest outcomes of the disorder.
Methods
We conducted a 9-year retrospective study of 46 children in 14 different centers across France to describe their clinical and laboratory presentations, therapeutic regimens, and kidney outcome.
Results
P-ANCA appeared to be a potential marker for higher relapse risk. Compared to adults, we found that ear-nose-throat presentations were frequent (45.7%) and more severe. Despite an evolution in the treatment management, kidney outcome remained poor with a substantial proportion of chronic kidney disease (54.8% at 1 year). Mortality stays low with 3 patients (6.5%) deceased at the end of our study.
Conclusion
Clinical presentation was as previously described and time to diagnosis remains long. P-ANCA is a statistically significant marker for increased relapse risk. We observed a modification in the treatment regimens over the past several years with a growing use of rituximab and a decreasing use of cyclophosphamide. Despite these changes, kidney outcome remains poor and prospective studies should be conducted to assess the most appropriate therapeutic modality for each patient.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
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.
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.
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.
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.
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.
Abstract
Background
Recommendations for management of Finnish-type congenital nephrotic syndrome (CNS) followed by many teams include daily albumin infusions, early bilateral nephrectomy, dialysis ...and transplantation. We aimed to assess the treatment and outcome of patients with CNS in France.
Methods
We conducted a nationwide retrospective study on 55 consecutive children born between 2000 and 2014 treated for non-infectious CNS.
Results
The estimated cumulative incidence of CNS was 0.5/100 000 live births. The underlying defect was biallelic mutations in NPHS1 (36/55, 65%), NPHS2 (5/55, 7%), PLCE1 (1/55, 2%), heterozygous mutation in WT1 (4/55, 7%) and not identified in nine children (16%). Fifty-three patients (96%) received daily albumin infusions from diagnosis (median age 14 days), which were spaced and withdrawn in 10 patients. Twenty children (35%) were managed as outpatients. Thirty-nine patients reached end-stage kidney disease (ESKD) at a median age of 11 months. The overall renal survival was 64% and 45% at 1 and 2 years of age, respectively. Thirteen children died during the study period including four at diagnosis, two of nosocomial catheter-related septic shock, six on dialysis and one after transplantation. The remaining 13 patients were alive with normal renal function at last follow-up median 32 months (range 9–52). Renal and patient survivals were longer in patients with NPHS1 mutations than in other patients. The invasive infection rate was 2.41/patient/year.
Conclusions
Our study shows: (i) a survival free from ESKD in two-thirds of patients at 1 year and in one-half at 2 years and (ii) a significant reduction or even a discontinuation of albumin infusions allowing ambulatory care in a subset of patients. These results highlight the need for new therapeutic guidelines for CNS patients.
Bardet‐Biedl syndrome (BBS) is a rare ciliopathy with variable retinal dystrophy, polydactyly, renal abnormalities, obesity, cognitive impairment, and hypogonadism. Biallelic pathogenic variants have ...been identified in 24 genes, leading to BBS in an autosomal recessive inheritance pattern. In this study, we investigated a cohort of 16 families (20 individuals) presenting with typical BBS originating from La Réunion Island using sequencing (Sanger and high‐throughput methods) and SNP array. In eight families (12 individuals) we identified the same ARL6/BBS3 variation c.535G > A, p.(Asp179Asn). Bioinformatics and functional analyses revealed an effect of this variant on the splicing of ARL6/BBS3. Owing to the relatively high frequency of this variant, a possible founder effect was suspected. Genotyping of six individuals revealed a common 3.8‐Mb haplotype and estimated the most recent common ancestor to about eight generations confirmed by the known genealogy. Knowledge of this founder effect modifies our diagnostic strategy and enables a personalized genetic counseling for patients from La Réunion Island. Being the first description of BBS patients from La Réunion Island, we could estimate its prevalence between ~1/45000 and ~ 1/66000 individuals.
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