An exceptional cause of polyuria-polydipsia syndrome in a 10-year-old boy.

Polyuria-polydipsia syndrome is a frequent symptom in pediatrics, primarily attributed to diabetes mellitus. In the context of diabetes insipidus, this syndrome can stem from central or nephrogenic factors. Sjögren's syndrome, an uncommon autoimmune disease in children, can affect multiple organs. Kidney involvement as described in adults is usually related to glomerular or tubular impairment, often linked to distal tubular acidosis. As a kidney involvement during childhood, Sjögren's syndrome has rarely been reported. Hereby, we present the case of Sjögren's syndrome revealed by polyuria-polydipsia syndrome in a 10-year-old boy.

Clinical and genetic characteristics of Tunisian children with infantile nephropathic cystinosis.

BACKGROUND: Nephropathic cystinosis is an autosomal recessive disease caused by a mutation in the CTNS gene which encodes cystinosin, a lysosomal cystine transporter. The spectrum of mutations in the CTNS gene is not well defined in the North African population. Here, we investigated twelve patients with nephropathic cystinosis belonging to eight Tunisian families in order to analyze the clinical and genetic characteristics of Tunisian children with infantile nephropathic cystinosis. METHODS: Clinical data were collected retrospectively. Molecular analysis of the CTNS gene was performed by Sanger sequencing. RESULTS: We describe a new splicing mutation c.971-1G > C in the homozygous state in 6/12 patients which seems to be a founder mutation. The reported deletion of 23nt c.771_793 Del (p.Gly258Serfs*30) was detected in a homozygous state in one patient and in a heterozygous compound state with the c.971-1G > C mutation in 3/12 patients. Two of 12 patients have a deletion of exons 4 and 5 of the CTNS gene. None of our patients had the most common 57-kb deletion. CONCLUSIONS: The mutational spectrum in the Tunisian population is different from previously described populations. Thus, a molecular diagnostic strategy must be implemented in Tunisia, by targeting as a priority the common mutations described in this country. Such a strategy will allow a cost-effective diagnosis confirmation as well as early administration of treatment with oral cysteamine. A higher resolution version of the Graphical abstract is available as Supplementary information.

Molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uraemic syndrome patients.

AIM: The aim of the present study was to characterize the molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uremic syndrome patients with low factor I levels. METHODS: Six adults and seven children were enrolled in this study. Complement factor I levels were assessed by a homemade sandwich ELISA and ranged between 12.5% and 60%. Genomic DNA was amplified by way of a polymerase chain reaction using intronic primers flanking the 13 coding exons. Sequencing of amplified products was carried out by the dye terminator sequencing method. Molecular study was performed on parental samples for three dead paediatric patients. The control group consisted of 100 healthy Tunisian donors. RESULTS: We identified a total of 13 substitutions and one insertion: seven in introns, four in exons and three in UTR. The new mutations were c.-132G > C, c.71 + 181 T > A in 5'UTR and intron 1, respectively. Three intronic polymorphisms were predicted to have impact on splicing events: c.482 + 6C > T, c.884-42_884-41insTTAAA (rs34422850) and c.1429 + 33 A > G (rs9998151). They were three missense mutations leading to a p.Ile 357Met, p.Ile416Leu and p.GLu548Gln. p.Ile 357Met was found in two patients and one relative. Half of the patients had associated mutation and/or polymorphisms. CONCLUSION: This is the first genetic study in Tunisian and Maghrebin atypical haemolytic and uraemic syndrome patients. The high occurrence of Ile357Met mutation may reflect a founding effect. Functional impact of the two new mutations c.-132G > C and c.71 + 181A > T have to be studied. Association of simultaneous genetic abnormalities may explain the variability of atypical haemolytic and uraemic syndrome, penetrance and disease phenotype.

Rituximab in The Management of Pediatric Steroid-Resistant Nephrotic Syndrome: A Systematic Review.

OBJECTIVES: To evaluate the efficacy and safety of rituximab in children with steroid-resistant nephrotic syndrome. STUDY DESIGN: A systematic review evaluating the efficacy and safety of rituximab in children with steroid-resistant nephrotic syndrome was performed. Data from studies, performed before April 2017 were collected, from MEDLINE, Cochrane Library, Scopus, and Web of Science. Study eligibility criteria included clinical trials and observational studies with a minimal sample size of 5 patients, regarding treatment with rituximab in children with steroid-resistant nephrotic syndrome. Independent extraction of articles by 2 investigators using predefined data fields was performed. RESULTS: We included 7 case series and 1 open-label randomized controlled trial. Among them, 3 studies were multicenter. A total of 226 patients were included. Mean age at onset was 5.6 ± 1.1 years. Mean number of rituximab administrations was 3.1 ± 1.1 infusions per patient. Remission was observed in 89 patients (46.4%). Remission was seen in 40.8% patients with initial steroid-resistant nephrotic syndrome and 52.8% patients with late steroid-resistant nephrotic syndrome. Good initial response to rituximab therapy was observed in 63.2% patients with minimal change nephrotic syndrome, 39.2% patients with focal and segmental glomerulosclerosis, 1 patient had diffuse mesangial hypercellularity, and 1 patient had IgM nephropathy. Sustained remission ranged from 18% to 93.7%. Five serious adverse events were observed. CONCLUSIONS: Rituximab exhibited a satisfactory profile regarding efficacy and safety indicating that this agent is a promising therapy for steroid-resistant nephrotic syndrome and should be further investigated by randomized clinical trials.

Evaluation of a CIAP session for students in Medicine, Pediatrics module.

BACKGROUND: Teaching by the Clarification, Illustration, Application and Participation of Students (CIAP) approach is a method of participatory pedagogy that helps active learning to help the learner understand and integrate the new Knowledge to be able to apply them. The objectives of this work were to describe the conduct of a CIAP session and to evaluate this method of learning among students. METHODS: The session took place in a room in the Forensic Medicine Department of the Charles Nicolle Hospital in Tunis on April 18, 2017 for 60 minutes. Our population was made up of DCEM2 students undergoing pediatrics and neonatology at the Charles Nicolle Hospital. The chosen topic was post-infectious acute glomerulonephritis. The assessment consisted in a written test given at baseline before the teaching sessions and repeated immediately afterwards. Students were also asked to grade the quality of the teaching received. RESULTS: In total, 13/22 students were present. Clarifications were given at the request of the students. The illustration showed capillary proliferation and extra-capillary proliferation. Clinical cases have sparked a lot of interaction. All the students participated in the session: seven of them participated actively, the other six were solicited to participate. Pre-test scores varied from 2/10 to 7/10. Post-test scores ranged from 4/10 to 10/10. The mean score for the pre-test was 4.61 ± 1.6 and, the mean score for the post-test was 8.23 ± 2.31 / 10, the difference being statistically significant (p = 0.03). For students, the choices of educational objectives were relevant and were achieved, the session was coherent with the professional reality and brought new knowledge. The majority of students felt that there was good interaction. All students were satisfied with listening to the teacher and her answers to their questions. All students reported that the CIAP session provided them with a better clarification of the theoretical course, a sufficient illustration, and enabled them to participate actively in teaching. The students reported that there was a good application of the theoretical course. CONCLUSION: The CIAP session improved student knowledge. The students were generally satisfied with this teaching.

Efficacy and Safety of Rituximab in the Management of Pediatric Systemic Lupus Erythematosus: A Systematic Review.

OBJECTIVES: To evaluate the efficacy and safety of rituximab for treating pediatric systemic lupus erythematosus (pSLE). STUDY DESIGN: We performed a systematic review to evaluate the efficacy and safety of rituximab in children with pSLE. Data from studies performed before July 2016 were collected from MEDLINE, the Cochrane Library, Scopus, and the International Rheumatic Disease Abstracts, with no language restrictions. Study eligibility criteria included clinical trials and observational studies with a minimal sample size of 5 patients, regarding treatment with rituximab in patients with refractory pSLE (aged <18 years at the time of diagnosis). Independent extraction of articles was performed by 2 investigators using predefined data fields. RESULTS: Twelve case series met the criteria for data extraction for the systematic review with a good quality assessment according to an 18-criteria checklist using a modified Delphi method. Among them, 3 studies were multicenter and 3 were prospective. The total number of patients was 272. Studies collected patients with active disease refractory to steroids and immunosuppressant drugs. Refractory lupus nephritis was the most common indication (33%). Acceptable evidence suggested improvements in renal, neuropsychiatric and haematological manifestations, disease activity, complement and anti-double stranded Desoxy-Nucleo-Adenosine, with a steroid-sparing effect. However, there was poor evidence suggesting efficacy on arthralgia, photosensitivity, and mucocutaneous manifestations of SLE in children. An overall acceptable safety profile with few major adverse events was shown. CONCLUSION: Rituximab exhibited a satisfactory profile regarding efficacy and safety indicating that this agent is a promising therapy for pSLE and should be further investigated.

HOGA1 Gene Mutations of Primary Hyperoxaluria Type 3 in Tunisian Patients.

BACKGROUND: Primary hyperoxaluria type 3 (PH3) is due to mutations in the recently identified 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. The aim of this study was to report three PH3 cases carrying mutations in HOGA1. MATERIALS AND METHODS: Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after sequencing of AGXT and GRHPR genes, which was negative. Also, a complete AGXT/GRHPR MLPA was performed in these patients in order to detect large deletions/insertions. RESULTS AND DISCUSSION: Two different HOGA1 gene mutations were identified: the p.Pro190Leu in a homozygous state and the p.Gly287Val in two patients in homozygous and heterozygous carriers. The median age at onset of clinical symptoms was 3.93 years. Most of the patients had a positive family history for recurrent urolithiasis. The p.Pro190Leu mutation was reported with impaired renal function at follow-up; however, the p.Gly287Val was presented with normal renal function. All patients were presented with urolithiasis, but only one had a nephrocalcinosis. CONCLUSION: This study expanded the number of PH3 patients from 63 to 66 cases. The p.Pro190Leu and the p.Gly287Val mutations found in this study can provide a first-line investigation in Tunisian PH1 patients.

X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations.

PURPOSE: X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. METHODS: Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2% peripheral B cells were enrolled. The search for BTK gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing. RESULTS: We identified 33 different mutations in the BTK gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5% vs. 85%). No strong evidence for genotype-phenotype correlation was observed. CONCLUSIONS: This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.

Contribution of ultrasound scans in the first episode of urinary tract infection in children.

Background - Vesicoureteral reflux (VUR) is a common pediatric urologic disorder. After the first urinary tract infection (UTI), imaging studies are recommended, starting with a renal ultrasound (US) and voiding cystourethrography (VCUG). We propose to determine whether abnormalities found on US can help indicate the necessity of VCUG in children after the first urinary tract infection. Methods - A retrospective study included all children admitted with their first episode of urinary tract infection from January 2007 to December 2012. Results - A total of 311 children were included. The median age was 2.5 years, 72.3% were female. VUR Prevalence was 14%.  Forty-four patients were found to have VUR on VCUG, giving a prevalence of 14%. Of these 44 patients, 11 had grade I reflux, 6 had grade II reflux, 3 had grade III reflux, 15had grade IV reflux, and 9 had grade V reflux. Ultrasound findings were positive for VUR in 43 patients, 19 of them had RVU. Twenty five patients had a normal ultrasound but showed VUR on VCUG (11 had grade I reflux, six grade II reflux, three grade III reflux and five grade IV reflux).  The sensitivity and specificity of ultrasound in suggesting VUR were 43% and 91%, respectively. The positive predictive value of ultrasound in suggesting VUR was 44%; the negative predictive value was 91%. Conclusion - Renal ultrasound findings are specific for VUR in children with a first UTI, but no sensitive. Clinicians should consider renal ultrasound results to take decision on whether or not to proceed with a VCUG in the investigation of a first episode UTI in young children.

Nephrotic syndrome in children: risk factors for steroid dependence.

Background - Most patients with idiopathic nephrotic syndrome are steroid-responsive, about 50% relapse and often become steroid-dependent and exposed to long-term steroid complications. The aim of this study was to determine predictive risk factors for steroid dependence using clinical and biological variables present at onset of the disease. It may be useful to adapt the therapeutic strategy. Methods - Retrospective hospital-based cohort study in the department of pediatric nephrology of Charles Nicolle, Tunis, between 2002 and 2012 included 52 children with idiopathic steroid-responsive nephrotic. Results - Risk factors for steroid dependency identified from univariate analysis were season of the first episode (winter or autumn) (p=0.008), hyperalpha2globulinemia>16g/l (p=0.028), hyperbeta2globulinemia >3g/l (p=0.003), hypercholesterolemia>10mmol/l (p=0.001), proteinuria>110mg/kg/day (p=0.05), time to achieve remission>9 days (p=0,0001). Logistic regression revealed that time to first remission and hypercholesterolemia>10mmol/l at first presentation were independent risk factors for steroid dependency. Conclusion - Time to first remission, hypercholesterolemia more than 10mmol/l at first presentation and a respiratory tract infection at first relapse are independent risk factors for steroid dependency.

Focal segmental glomerulosclerosis in children.

Background Focal segmental glomerulosclerosis (FSGS) represents 20% of nephrotic syndrome in children. The clinical course and prognosis is heterogeneous in children. The aim of this study was to analyze treatment and outcome of children with FSGS. Methods This retrospective study was conducted in the Department of Pediatrics in Charles Nicolle Hospital during a 15-year period (1996-2010). Results There were 30 children, 16 boys and 14 girls. The mean age was 7 ± 4 years. Nephrotic syndrome was observed in 26 patients, hematuria was noticed in 2 patients and renal insufficiency was detected in 2 patients at presentation. FSGS, not otherwise specified, was the predominant variant. All patients with nephrotic syndrome were treated with steroids. Only three patients responded to it. Twenty one patients were treated with cisclosporin A and this resulted in a 57% complete remission and a 24% partial response. Cyclophosphamide was administered to 6 patients and engendered a 50% complete remission. Six patients were treated with mycophenolate mophetil and showed no response in all cases. Renal insufficiency has been developed in 12 children. Conclusion Results from this study showed that the majority of children with FSGS achieve a high sustained remission rate with ciclosporine A.

Peritoneal dialysis: Experience of the department of pediatrics of the hospital Charles Nicolle of Tunis.

Introduction Peritoneal dialysis (PD) is still the most common modality used in treatment for children with End Stage Renal Disease (ESRD). The objective of this study was to identify the epidemiological, clinical, and microbiological factors affecting the outcome of PD. Methods In this study, we retrospectively reviewed the records of 85 patients who were treated with DP for the last ten years (from January 2004 to December 2013) in the Department of Pediatrics in Charles Nicolle hospital, Tunis. Results The mean duration of PD was 18.1±12 months (3.5-75 months). The average age of PD onset was 9.3±5.7 years (29 days-23 years). The sex ratio was 1.5. In a significant number of cases with ESRD, the primary cause is Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT). Seventy-four of our patients (87%) had been treated with Automated PD. The average time between catheter placement and PD commencement was 3.9±4.6 days. Catheter change was 1.62 (1-5). Sixty-one patients (71.8%) had experienced at least one episode of peritonitis. The most frequently isolated organisms was the Gram-positive bacteria (61%). Survival rates without peritonitis at 12th, 24th and 36th months were 40%, 32% and 18%, respectively. Transition to permanent hemodialysis was required in 66% of patients. Conclusion Considering the important incidence of peritonitis in our patients, it is imperative to establish a targeted primary prevention.

Nephrocalcinosis in Tunisian children.

Background Nephrocalcinosis is rare in children. Its etiologies are multiple. The aim of this study was to analyze the etiology of nephrocalcinosis in Tunisian children. Methods This retrospective study was conducted in the department of pediatrics in Charles Nicolle Hospital during a period of 10 years (2001-2010). Results There were 40 children. The mean age was 3.5 years. The most common signs and symptoms at presentation were growth retardation (42.5%) and hematuria (53.8%). At presentation, renal failure was detected in 70% of patients. The diagnosis of nephrocalcinosis was performed by ultrasonography. The etiology of nephrocalcinosis included primary hyperoxaluria type 1 (65%) and distal renal tubular acidosis (20%). A progression to renal insufficiency was observed in 18 cases. Conclusion Primary oxaluria is the principal cause of nephrocalcinosis; early diagnosis and treatment are mandatory as they help limiting renal function deterioration.

Mycophenolate mofetil in treatment of childhood steroid-dependent nephrotic syndrome.

OBJECTIVES: To establish the efficacy of mycophenolate mofetil (MMF) in steroid dependent nephrotic syndrome and to determine the predictive factors for a good response. METHODS: retrospective hospital-based cohort study in the department of pediatric of Charles Nicolle hospital, between 2005 and 2012 included 30 children with steroid-dependent nephritic syndrome who were treated with MMF. RESULTS: A total of 30 patients (20 boys and 10 girls) were included. The mean age at the time of diagnosis was 5.45 years and treatment with MMF was performed at a mean age of 10.84 years. Side effects of steroid were found in 17 patients. Four patients had renal impairment (ciclotoxicity). The evolution of the disease was 5.45 years. The average rate of relapse was 1.75 relapses / year. The minimum dose of corticosteroids was 0.74 mg / kg / day. During MMF therapy, the average rate of relapse was 0.45 relapses / year (p<0.0001). The average residual steroid dose was 0.2 mg/kg/ day. Responding patients were younger at the onset of MMF (8.57 versus 12.83, p=0.009), had a short development period (3.75 vs 7.03 years, p=0.05), had not received cyclosporine (p=0.02). CONCLUSION: MMF allows steroid sparing and reduces the number of relapse. It is more effective than the patients are young, with short disease outcome and had not previously been treated with cyclosporine.