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BACKGROUND: Alport syndrome is a genetic disorder affecting the kidneys, ears, and eyes, causing chronic kidney disease, sensorineural hearing loss, and ocular abnormalities. It results from pathogenic variants in the COL4A3, COL4A4, or COL4A5 genes, with different inheritance patterns: X-linked from COL4A5 variants, autosomal recessive from homozygous variants in COL4A3 or COL4A4, digenic from variants in both COL4A3 and COL4A4, and autosomal dominant from heterozygous variants in COL4A3 or COL4A4. METHODS: We analyzed 45 patients with Alport syndrome from 11 Tunisian families to determine their clinical and genetic characteristics. Clinical data were collected retrospectively, and whole-exome sequencing was conducted on one patient from each family. Sanger sequencing validated pathogenic variants, and cascade screening extended the analysis to 53 individuals. RESULTS: We identified nine likely pathogenic variants among 11 index cases: six novel and three known variations. Of these, five were in COL4A3, and four were in COL4A5, with variants including frameshift, nonsense, missense, and alternative splicing. Most variations affected the Gly-XY codon. Among the 45 clinically identified siblings, 30 tested positive for Alport syndrome. The cascade screening identified 3 additional affected individuals, 10 unaffected siblings, and 10 unaffected parents. The mode of inheritance was autosomal recessive in six families and X-linked in four families. CONCLUSIONS: This study is the first to screen the mutational spectrum of Alport syndrome in Tunisia. It reveals novel pathogenic variants and suggests that autosomal recessive inheritance may be more common in the Tunisian population than X-linked inheritance, contrary to existing literature.
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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.
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Fallo Renal Crónico , Insuficiencia Renal , Masculino , Femenino , Humanos , Niño , Adulto , Vejiga Urinaria , Estudios Retrospectivos , UrodinámicaRESUMEN
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.
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Acidosis Tubular Renal , Hipopotasemia , Nefrocalcinosis , Compuestos Organometálicos , ATPasas de Translocación de Protón Vacuolares , Niño , Humanos , Lactante , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/epidemiología , Acidosis Tubular Renal/genética , Túnez/epidemiología , Hipopotasemia/etiología , Hipopotasemia/genética , Nefrocalcinosis/epidemiología , Nefrocalcinosis/genética , Estudios Retrospectivos , Estudios de Asociación Genética , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
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.
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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.
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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.
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Acidosis Tubular Renal , Nefrocalcinosis , ATPasas de Translocación de Protón Vacuolares , Niño , Humanos , Acidosis Tubular Renal/complicaciones , Acidosis Tubular Renal/epidemiología , Acidosis Tubular Renal/genética , Nefrocalcinosis/epidemiología , Nefrocalcinosis/etiología , Estudios Retrospectivos , Deshidratación/complicaciones , Trastornos del Crecimiento , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
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.
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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.
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Calidad de Vida , Urodinámica , Niño , Humanos , Lactante , Masculino , Estudios Retrospectivos , Uretra/cirugía , Vejiga UrinariaRESUMEN
Cutaneous manifestations of childhood COVID-19 differ from those of adults. Maculopapular rash is not specific and could be mistaken with other viral exanthema. A nasopharyngeal swab is strongly recommended to confirm the possible COVID-19 diagnosis.
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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.
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Pediatría , Estudiantes de Medicina , Niño , Razonamiento Clínico , Evaluación Educacional , Humanos , AprendizajeRESUMEN
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.