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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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Mariem El Younsi [sup.1] , Médiha Trabelsi [sup.2] , Sandra Ben Youssef [sup.3] , Inès Ouertani [sup.2] , Yousra Hammi [sup.3] , Ahlem Achour [sup.2] , Faouzi Maazoul [sup.2] [...]

Introduction: Nephronophthisis (NPHP) is a tubulointerstitial kidney disorder with an autosomal recessive inheritance pattern. Its genetic heterogeneity contributes to phenotype variability. The most frequent etiology of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. This study aimed to evaluate the genotype-phenotype correlation in NPHP1 gene mutation. Methods: A multicenter retrospective study was performed over 20 years from 1998 to 2018 to describe the clinical, biological, and radiological features associated with the large deletion NPHP1 gene in 32 patients. Results: The incidence of NPHP1 was 1.6/204041. Eighty-one percent of our patients were born out of consanguineous marriages. The mean age at diagnosis was 14 ± 7 years. The patients were divided into three groups: isolated nephronophthisis (72%), syndromic nephronophthisis (19%), and patients without recognizable syndrome (9%). Intrafamilial and geographical variability was observed in syndrome diagnoses and in age at the onset of CKD stage 5. Genotype frequency varied between 50% and 100% in genealogical data. Juvenile (47%), adolescent (37%), and adult (13%) clinical forms have been distinguished by the onset of CKD stage 5. The five-year survival rate of renal transplantation was 80%. Conclusion: Given the broad clinical spectrum of NPHP1 associated with the large deletion of the NPHP1 gene, no genotype-phenotype correlation could be established. [ABSTRACT FROM AUTHOR]

Le syndrome de Protéeest une maladie très rare, se traduisant par une croissance excessive pouvant toucher différents organes et tissus de l'organisme. Ses complications sont dominées par les complications thromboemboliques et tumorales. Nous rapportons le cas d'un malade suivi pour un syndrome de Protée qui présentait un gigantisme des membres supérieurs avec une macrodactylie et une hypertrophie du thorax ainsi qu'une scoliose. [ABSTRACT FROM AUTHOR]

Dyskeratosis congenita (DC) is a very rare inherited disorder. It is caused by dysfunction of telomere maintenance. It involves RNA telomerase components relevant to various mutations leading to a classic triad of physical findings consisting of nail dystrophy of the hands and feet, mucosal leukoplakia, and reticular pigmentation of the skin, most commonly on the head, neck, and trunk. Bone marrow failure along with pulmonary complications and malignancies are all common causes of premature death in patients with DC as well as other abnormalities. We report a new case of DC with impure nephrotic syndrome relevant to histopathologic signs of a diffuse mesangial sclerosis, leading to an early end-stage renal disease. Challenges remain to understand the diverse spectrum of DC especially in children. To the best of our knowledge this is the first case of DC associated to diffuse mesangial sclerosis. [ABSTRACT FROM AUTHOR]

Dyskeratosis congenita (DC) is a very rare inherited disorder. It is caused by dysfunction of telomere maintenance. It involves RNA telomerase components relevant to various mutations leading to a classic triad of physical findings consisting of nail dystrophy of the hands and feet, mucosal leukoplakia, and reticular pigmentation of the skin, most commonly on the head, neck, and trunk. Bone marrow failure along with pulmonary complications and malignancies are all common causes of premature death in patients with DC as well as other abnormalities. We report a new case of DC with impure nephrotic syndrome relevant to histopathologic signs of a diffuse mesangial sclerosis, leading to an early end-stage renal disease. Challenges remain to understand the diverse spectrum of DC especially in children. To the best of our knowledge this is the first case of DC associated to diffuse mesangial sclerosis. [ABSTRACT FROM AUTHOR]

Background: Childhood vesico-sphincteric disorders are the cause of functional and psychological disability. They are also responsible for serious uronephrologic complications akin to neuro-bladder complications. In this study, we looked for the clinical manifestations linked to these disorders as well as the paraclinical and urodynamic anomalies and their therapeutic management., Methods: We carried out a retrospective and descriptive study of patients with vesico-sphincteric disorders, followed in the pediatrics department of Charles Nicolle hospital in Tunis., Results: In total 26 patients were included in our study. The median age at the first consultation in a pediatric nephrology department was 9 years (IQR 25 = 6 years; IQR 75 = 11 years). There was a predominance of girls: 19 boys and 43 girls. The filling phase and the voiding phase were dominated by the combination of three or more symptoms. Bladder tenderness was reduced in 12% of cases. Nineteen percent of patients reported post micturition dribble in the post-voiding phase. The flow rate curve was polyphasic in 36% of cases and flat in 11% of cases. The median of the post void residual was 62, 2 mL (IQR 25 = 25 mL; IQR 75 = 102 mL). Cystometry showed reduced bladder sensation in 14% of cases, detrusor overactivity in 65% of cases, bladder hypocontractility in 8% of cases, hypocompliant bladder in 42% of cases and small capacity in 88% of cases. Sphincter dysynergia was noted in 34% of patients. Anticholinergics were the most used in the treatment of disorders (53%). Renal failure was noted in 45% of the patients of which 11% had end-renal stage failure. During follow-up 16% of our patients required kidney replacement therapy., Conclusion: Given the seriousness of vesico-sphincteric disorders in children and the late discovery in the majority of cases at the complication stage, targeted primary prevention must be carried out based on continuous training of primary care physicians to minimize the appearance of complications involving the functional and vital prognosis of these children.

Introduction: Distal renal tubular acidosis (dRTA) is a rare genetic disorder due to the incapacity of the α intercalated cells to excrete protons in the collecting duct. This impaired distal acidification of urine leads to a chronic hyperchloremic metabolic acidosis with a normal plasma anion gap, hypokalemia, and hypercalciuria with hypocitraturia causing nephrocalcinosis. Primary dRTA is inherited either as an autosomal dominant (SLC1A4 gene) or autosomal recessive trait (ATP6V0A1/ATP6V1B1 genes)., Aim: To analyze the genotype-phenotype correlation of dTA in Tunisia., Methods: In this study we present all available data of patients followed in our center for dRTA over the last 28 years and who had a genetic study. This was a retrospective descriptive study from January 1991 to December 2018, conducted in the Pediatrics Department of the Charles Nicolle Hospital in Tunis., Results: Twenty-five cases of dRTA were collected and were offered genetic analysis to confirm the diagnosis. The molecular mutation was confirmed in 13 patients of whom 11 had homozygous mutations in ATP6V1B1(G1) and 2 had homozygous mutations in ATP6V0A4(G2). Median age of diagnosis was 8.9 months. Severe growth retardation was documented in nine children with mutations in ATP6V1B1, in eight children with no genetic mutation and in the two patients with a mutation in ATP6V0A4. All children were found to have metabolic acidosis at initial presentation. Hypokalemia was found in 19 children. All patients were polyuric. Twenty-two patients had nephrocalcinosis (88%). The treatment was based on alkali prescription and substitution of potassium chloride. Sensorineural hearing loss (SNHL) was documented in 12 children. At the last consultation, 14 patients had chronic kidney disease (CKD) stage 2 or higher, 8 of whom were in the group with negative genetic analysis., Conclusion: According to the early onset in patients, the recessive mode seems to be the mode of transmission in Tunisia. dRTA was long considered to not affect renal function, but we note a decline in eDFG.

Introduction: The distal renal tubular acidosis of children is characterized by hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria and nephrocalcinosis. It is secondary to the inability of alpha intercalar cells of the distal tubule to acidify urine of genetic origin., Objective: To analyse the epidemiological aspects of distal tubular acidosis in Tunisia and study its evolutionary profile., Patients and Methods: We conducted a retrospective descriptive study involving 44 patients followed at the paediatrics department of the Charles Nicolle Hospital in Tunis for 28 years (1991-2018)., Results: The most common discovery circumstances were growth retardation (88.6%), dehydration (56.8%), ployuro-polydipsic syndrome (47.7%), vomiting (40.9%) and nephrocalcinosis (38.6%). Growth retardation was found in 52.3% of patients. Dehydration was diagnosed in 59.1% of patients on the first exam. Polyuria was constant with an average diuresis of 8 cc/kg/h. All patients had the complete form of distal renal tubular acidosis with an average alkaline reserve of 11.1 mmol/L. Nephocalcinosis was found in 77.3% associated with nepholithiasis in 22.7%. Twenty-four patients had sensorineural deafness, nine of whom had ATP6V1B1/2p13 mutation. The ATP6V0A4/7q33-34 mutation was present in two patients. We used a high alkaline treatment dose with an average maintenance dose of 8.17 mmol/kg/24 hours. In the long term, stunting persisted in 34% of patients. The mean of creatinine's clearance at the last evaluation was 89.38 mL/min/1.73 m 2 SC with stage 2 of chronic kidney disease in 50% of patients., Conclusion: Distal renal tubular acidosis has long been considered a benign pathology but is responsible for a progressive decline in GFD. Adequate metabolic control is needed to stabilize kidney function., (Copyright © 2022 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Background: Bladder dysfunction may be associated with valves of the posterior urethra. Their evaluation by urodynamic assessment is an important parameter for the therapeutic management. The objective of our study was to study the contribution of urodynamic assessment in the management of valves of the posterior urethra of the child., Methods: Our study was descriptive, retrospective, involving 43 children with posterior urethral valves (PUV), followed at the pediatric ward at Charles Nicolle Hospital in Tunis from January 1995 to December 2015. All the children had an urodynamic assessment after valves of the posterior urethra treatment., Results: The mean age was 15.8 months. Preoperatively, creatinine clearance was below 60 ml / min in 32 patients (74%). The worsening of renal function was noted in 32 (74%). A significant post-voiding residue proved in 34 patients (79%). Cystometry revealed a hypo compliant bladder in 24 (56%), low bladder capacity in 42% of cases; a hypertonic detrusor in 37% of cases. Bladder sphincter dyssynergia was diagnosed in 6 patients. Like urodynamic assessment data, bladder enlargement associated with a Mitrofanoff-type shunt was indicated and performed in 3 patients (7%)., Conclusion: Through our study, the urodynamic profile made it possible to specify the type of vesico-sphincter dysfunctions persistent in patients operated for PUV, and subsequently to adapt the therapeutic conduct in these patients. Given the lack of management and the consequences on the health of the child as well as on his quality of life, reflections on the preventive and therapeutic approach after PUV treatment are necessary.

Introduction: Learning clinical teaching is an alternative to traditional forms of teaching. Its objective is to lead the student to acquire a relevant diagnostic approach by developing a clinical reasoning., Aim: To evaluate these sessions in Pediatrics, with students in the second cycle of medical study., Methods: A session on the topic of "stunting" was scheduled as a CRL with second cycle of medical studies 2 (SCMS2) students during their Pediatrics internship, with a pre and post-test administered and a self-administered questionnaire., Results: Two groups of students that included twenty-three students participated in the session. Pre-test scores ranged from 0/10 to 6.8 / 10 and post-test scores from 6.5 / 10 to 9/10. The average pre- and post-test scores, were respectively 4.26 ± 1.37/10 and 7.35 ± 0.7 / 10 (P <0.001). Twenty-two students reported their overall satisfaction with teaching. The overall rating score was 4.39 ± 0.49/ five points. The average of the ratings for new knowledge delivery, achievement of educational objectives, interaction and participation were greater than 4.3 / 5., Conclusion: This form of small group learning seems to have legitimacy in Pediatric education.

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.

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.

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.

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.

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.

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.

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.