Functional vesico-sphincteric disorders in children: clinical, urodynamic and evolutionary profile / Les troubles vésico-sphinctériens fonctionnels de l'enfant : profil clinique, urodynamique et évolutif

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: Les troubles vésico-sphinctériens de l'enfant sont à l'origine d'un handicap fonctionnel et psychologique. Ils sont également responsables de complications uronéphrologiques graves s'apparentant aux complications des neuro-vessies. Le but de cette étude était d'étudier les manifestations cliniques liées à ces troubles ainsi que les anomalies paracliniques et urodynamiques et leur prise en charge thérapeutique. Méthodes: Dans ce travail, nous avons effectué une étude rétrospective et descriptive à propos de patients porteurs de troubles vésico-sphinctériens, suivis dans le service de pédiatrie de l'hôpital Charles Nicolle de Tunis. Résultats: Au total, 62 enfants ayant des troubles vésico-sphinctériens fonctionnels ont été inclus dans notre étude. La médiane d'âge à la première consultation dans un service de néphrologie pédiatrique était de 9 ans (IQR 25 = 6 ans ; IQR 75 = 11 ans). Il y avait une prédominance féminine : 19 garçons et 43 filles. La phase de remplissage et la phase mictionnelle étaient dominées par l'association de trois symptômes ou plus. La sensibilité vésicale était diminuée dans 12 % des cas. Dix-neuf pour cent des patients rapportaient des gouttes retardataires dans la phase post-mictionnelle. La courbe de débimétrie était polyphasique dans 36 % des cas et plate dans 11 % des cas. La médiane du résidu post-mictionnel était de 62,2 mL (IQR 25 = 25 mL ; IQR 75 = 102 mL). La cystomanométrie a montré une sensibilité vésicale réduite dans 14 % des cas, une hyperactivité détrusorienne dans 65 % des cas, une hypocontractilité vésicale dans 8 % des cas, une vessie hypocompliante dans 42 % des cas et de petite capacité dans 88 % des cas. Une dyssynergie vésico-sphinctérienne a été notée chez 34 % des patients. Les anticholinergiques étaient les plus utilisés dans le traitement des troubles (53 %). Une insuffisance rénale était notée dans 45 % des cas dont 11 % au stade terminal. Au cours du suivi, 16 % de nos patients avaient nécessité le recours à l'épuration extra-rénale. Conclusion: Compte tenu de la gravité des troubles vésico-sphinctériens chez l'enfant et la découverte tardive dans la majorité des cas au stade de complications, une prévention primaire ciblée doit être menée en s'appuyant sur une formation continue des médecins de première ligne pour minimiser l'apparition des complications mettant en jeu le pronostic fonctionnel et social de ces enfants.

Mesenteric Arterial Thrombosis Revealing Relapse of Nephrotic Syndrome in Young Women.

Background: Nephrotic syndrome (NS) is associated with a hypercoagulable state and may be complicated by thrombotic events. Venous thrombosis is well-acknowledged, while arterial thrombosis is rather unusual. Case Presentation: We present the case of a 20-year-old woman with a 12-year history of idiopathic NS revealed by extensive cerebral venous thrombosis with pulmonary embolism treated with anticoagulation therapy and oral corticosteroid therapy followed by mycophenolate mofetil (MMF). The thrombophilia assessment did not show any abnormalities. The evolution was marked by the occurrence of several NS relapses controlled by oral corticosteroid therapy until 2017. Subsequently, the patient had not presented a relapse of her disease. The anticoagulant treatment and the MMF were therefore stopped. One year later, the patient presented with severe diffuse acute abdominal pain associated with postprandial vomiting and bilateral lower limb edema. Laboratory results confirmed a NS relapse. An abdominal CT scan revealed acute thrombosis of the superior mesenteric artery with acute mesenteric ischemia. Intraoperative exploration showed mesenteric ischemia with extensive necrosis of the small intestine making their resections incompatible with life. The patient died after 48 hours. Conclusion: Mesenteric arterial thrombosis, which is a rare but life-threatening NS complication, should always be considered, especially in the case of acute non-specific digestive symptoms.

Tuberculosis and Takayasu arteritis: a case report.

BACKGROUND: Takayasu arteritis is a rare and chronic granulomatous vasculitis that affects the large vessels. Takayasu arteritis targets the aorta and its branches and is still of unknown etiology. It often affects female patients under 50 years of age. A relationship between Takayasu arteritis and tuberculosis has been suggested for a long time. CASE PRESENTATION: We report a severe case of Takayasu arteritis in a 10-year-old Tunisian child revealed by renovascular hypertension with concomitant pulmonary tuberculosis. CONCLUSIONS: Our patient is among only a few cases of Takayasu arteritis published worldwide affecting young infants and adolescents, which underlines the strong relationship between Takayasu arteritis and tuberculosis.

Genotype-Phenotype correlation of distal renal tubular acidosis in Tunisia.

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.

Phenotype Spectrum in Tunisian Population with NPHP1 Deletion.

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.

[Epidemiological, clinical and evolutionary particularities of primary distal tubular acidosis in Tunisian children]. / Particularités épidémiologiques, cliniques et évolutives de l'acidose tubulaire distale primitive chez l'enfant tunisien.

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 m2 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.

Systemic lupus erythematosus-related acute pancreatitis: An exceptional form with severe exocrine and endocrine pancreatitic failure in a Tunisian child.

Acute pancreatitis may be the first manifestation in systemic lupus erythematosus or occur during evolution. It is a rare complication, which is often associated with other visceral manifestations. Outcome is usually favorable but can be serious. We report a case of a 17-year-old girl with a past history of systemic lupus erythematosus who developed acute pancreatitis revealed by abdominal pain. Elevated serum amylase and lipase levels and pancreatic enlargement on tomography confirmed the diagnosis. Although high-dose corticosteroid was prescribed, the patient died from a refractory diabetic ketoacidosis.

WDR73-related galloway mowat syndrome with collapsing glomerulopathy.

Galloway-Mowat syndrome (GAMOS [MIM 251300]) is a rare autosomal recessive disorder that manifests as a combination of nephrotic syndrome, brain abnormalities and developmental delay. It is a clinically and genetically heterogeneous disease. The WDR73 variations are associated with GAMOS1. Here we report two consanguineous families affected by GAMOS1. In the first family, three sisters are affected and in the second family, only one index case is identified. They all show a nephrotic syndrome, a neurological involvement and a collapsing glomerulopathy. The analysis of mutations of WDR73 revealed a new homozygous missense mutation NM_032856.3 c.293T > C; p.(Leu98Pro) in two patients from the first family, and a new homozygous missense mutation NM_032856.3: c.767G > A; p.(Arg256Gln) in the second one. This study extended the clinical and molecular spectrum of GAMOS1 with other cases associated with collapsing glomerulopathy and two novel WDR73 variations that are most likely pathogenic.

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.