Mutant WD-repeat protein in triple-A syndrome.

Triple-A syndrome (MIM 231550; also known as Allgrove syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency, achalasia of the oesophageal cardia and alacrima. Whereas several lines of evidence indicate that triple-A syndrome results from the abnormal development of the autonomic nervous system, late-onset progressive neurological symptoms (including cerebellar ataxia, peripheral neuropathy and mild dementia) suggest that the central nervous system may be involved in the disease as well. Using fine-mapping based on linkage disequilibrium in North African inbred families, we identified a short ancestral haplotype on chromosome 12q13 (<1 cM), sequenced a BAC contig encompassing the triple-A minimal region and identified a novel gene (AAAS) encoding a protein of 547 amino acids that is mutant in affected individuals. We found five homozygous truncating mutations in unrelated patients and ascribed the founder effect in North African families to a single splice-donor site mutation that occurred more than 2,400 years ago. The predicted product of AAAS, ALADIN (for alacrima-achalasia-adrenal insufficiency neurologic disorder), belongs to the WD-repeat family of regulatory proteins, indicating a new disease mechanism involved in triple-A syndrome. The expression of the gene in both neuroendocrine and cerebral structures points to a role in the normal development of the peripheral and central nervous systems.

Small bowel obstruction by an anomalous congenital band.

We report a case of a 3-year-old boy who presented with symptoms and signs of intestinal obstruction. The patient reported no previous history of abdominal surgery or trauma while clinical and radiographic examinations were not diagnostic. An open laparotomy was subsequently performed and the intraoperative findings were consistent with a congenital band extending from the antimesenteric wall of the jejunum to the root of mesentery. The band was ligated and divided with an uneventful postoperative course. Congenital bands are extremely rare. Their exact incidence is still unknown. This case, therefore, represents an unusual surgical problem in a child in which the diagnosis was clinically unexpected.

Surgical management of recto-sigmoid Hirschsprung's disease.

INTRODUCTION: Over the years, the surgical management of recto-sigmoid Hirschsprung's disease (HD) has evolved radically and at present a single stage transanal pull-through can be done in suitable cases, which obviates the need for multiple surgeries. AIM: The aim of this paper was to evaluate the role of transanal pull-through in the management of recto-sigmoid HD in our institution. MATERIAL AND METHODS: A retrospective analysis (between January 2003 and December 2009) was carried out on all cases of Hirschsprung's reporting to unity of pediatric surgery of Tunis Children's Hospital that were managed by transanal pull-through as a definitive treatment. All selected patients including neonates had an aganglionic segment confined to the rectosigmoid area, confirmed by preoperative barium enema and postoperative histology. Twenty-six children (86%) had their operation done without construction of prior colostomy. RESULTS: Transanal pull-through was performed in 31 children. Mean operating time was 150 minutes (range 64 to 300 minutes). No patients required laparotomy because all patients including neonates had an aganglionic segment confined to the rectosigmoid area. Blood loss ranged between 20 to 56 ml without blood replacement. Since all children were given an epidural caudal block, the requirement of analgesia in these cases was minimal. Postoperative complications included perianal excoriation in 7 out of 31 patients lasting from 3 weeks to 6 months. Complete anorectal continence was noted in 21 of 31 (67%) children in follow up of 3-5 years. CONCLUSIONS: Transanal endorectal pull-through procedure for the management of rectosigmoid HD is now a well-established and preferred approach. Parental satisfaction is immense due to the lack of scars on the abdomen. As regards the continence, a long-term follow-up is necessary to appreciate better the functional results of this surgery.

Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome.

Triple A syndrome (Allgrove syndrome, MIM No. 231550) is a rare autosomal recessive disorder characterised by ACTH-resistant adrenal insufficiency, achalasia of the cardia, and alacrimia. The triple A gene has been previously mapped to chromosome 12q13 in a maximum interval of 6 cM between loci D12S1629 and D12S312. Using linkage analysis in 12 triple A families, mostly originating from North Africa, we confirm that the disease locus maps to the 12q13 region (Zmax = 10.89 at theta = 0 for D12S1604) and suggest that triple A is a genetically homogeneous disorder. Recombination events as well as homozygosity for polymorphic markers enabled us to reduce the genetic interval to a 3.9 cM region. Moreover, total linkage disequilibrium was found at the D12S1604 locus between a rare allele and the mutant chromosomes in North African patients. Analysis of markers at five contiguous loci showed that most of the triple A chromosomes are derived from a single founder chromosome. As all markers are located in a 0 cM genetic interval and only allele 5 at the D12S1604 locus was conserved in mutant chromosomes, we speculate that the triple A mutation is due to an ancient Arabian founder effect that occurred before migration to North Africa. Since we also found linkage disequilibrium at D12S1604 in two patients from Southern Europe (France and Spain), the founder effect might well extend to other Mediterranean countries. Taking advantage of a YAC contig encompassing the triple A minimal physical region, the triple A gene was mapped to a 1.7 Mb DNA fragment accessible to gene cloning.

[Bilateral stenosing ureteritis in Henoch-Schnlein purpura]. / Urétérite sténosante bilatérale au décours du purpura rhumatoïde de Henoch-Schönlein.

BACKGROUND: Ureteral complications in Henoch-Schonlein's purpura are rare. They may post difficult problems of diagnosis. CASE REPORT: Bilateral uretal stenosis revealed by low back pain, macroscopic hematuria, leukocyturia and renal failure appeared 15 days after the onset of Henoch-Schönlein purpura in a 14-year-old boy. It was confirmed by ultrasonography; intravenous pyelography showed stenosis of both proximal uretera associated to bilateral hydronephrosis. Treatment with corticosteroids relieved the symptoms and normalized the renal function in restoring patency of both ureters. Nevertheless, the patient was still suffering from mild bilateral hydronephrosis and bilateral renal lithiasis, 2 years later. CONCLUSIONS: Macroscopic hematuria and renal failure, usually indicative of renal involvement in Henoch-Schönlein syndrome can be the first manifestations of the ureteritis exceptionally seen in this vasculitis.

[Urinary calculi in children: contribution of anamnesis, biological exploration and physical analysis of calculi to the etiological diagnosis]. / La lithiase urinaire de l'enfant: contributions de l'anamnèse, de l'exploration biologique et de l'analyse physique des calculs au diagnostic étiologique.

BACKGROUND: It is always of importance to define the cause of urinary calculi disease in children to prevent recurrence and possible impairing of renal function. Nevertheless, etiology is not always easy to prove and must be deduced from both clinical and biological arguments. PATIENTS AND METHODS: The aim of this prospective study including 39 Tunisian children with urinary stones was to identify etiology and stone risk factors and detail the part of clinical and biological data and results of physical analysis of stones in determining the cause of the stone. RESULTS: In 31 cases among 39, clinical and biological data were not sufficient to identify clearly the stone etiology. When considering the structure and stone composition, the cause of the stone could be determined in 97.4% of the cases. An inherited disease was found responsible for the stone in 11 children, urinary tract infection in 13 cases, idiopathic hypercalciuria in nine cases and a nutritional deficiency disease in seven cases. In one case, polycystic kidney disease with metabolic risk factors could explain the stone process. No precise etiology was found in one case. Among infection stones, struvite stones could be related to urea-splitting bacteria while other calculi, containing whitlockite and protein matrix could be related to other micro-organisms. Earlier severe chronic diarrhoea episodes were noted in six among seven children presenting stones with a nucleus mainly composed of ammonium urate. CONCLUSION: Clinical data, biological data from both urine and blood of the patients and also the structure and composition of the stones are needed to identify the cause of urinary calculi. Such a procedure could provide the stone etiology in most cases.

[An exceptional combined malformation: duplication of the lower urinary tract, the vulva and the posterior intestine]. / Une association malformative exceptionnelle: duplication du bas appareil urinaire, de la vulve et de l'intestin postérieur.

The authors report the case of a 6 year old girl with bladder duplication, urethral duplication, genital system duplication associated with colonic duplication and low double anorectal anomalies. This patient presented two hemivertebrae at T9 and T11. This girl died a few days after admission from internal obstruction and septicemia. The embryological features especially the possibility of associating two different embryopathogenic mechanisms in the pathogenesis of this combined malformation (Split notochord syndrome and fissure of the urogenital system), and diagnostic and therapeutic aspects are studied in relation to this case and a review of the literature.

[Hereditary nature of nephroblastoma. Apropos of a case of 3 siblings]. / L'hérédité du néphroblastome. A propos d'une fratrie de trois membres atteints.

Three nephroblastomas, including one bilateral tumour, have been detected in three children belonging to the same family and born from a consanguinous marriage. The clinical and diagnostic particularities compared to non familial "sporadic" nephroblastomas are studied. The pathogenesis with the incidence of chromosomal anomalies, the diagnosis and the frequency of bilateral diseases along with the associated deformities and a non invasive therapeutic attitude are discussed.

[Bilateral neuroblastoma. Study of 5 cases and review of the literature]. / Néphroblastomes bilatéraux. Etude de cinq observations et revue de la littérature.

Five cases of bilateral nephroblastoma out of total of 99 cases have been observed during a period of 18 years at the Children's Hospital of Tunis (5%). The frequency of associated anomalies, the familial incidence, the young age of the patients are underlined. The main therapeutic modalities and prognosis are envisaged.

[Congenital mesoblastic nephroma. Apropos of a prenatally diagnosed case]. / Le néphrome mésoblastique congénital. A propos d'une observation diagnostiquée en prénatal.

The authors analyse this case and those published in the literature (115 cases) and the relationship to Wilm's tumor. The histologic characteristics of this tumor and its benign course indicate surgical treatment without any adjuvant treatment.

[Video-assisted thoracic surgery of hydatid cysts of the lung in children]. / La chirurgie thoracique vidéo-assistée des kystes hydatiques du poumon chez l'enfant.

10 children between 3 and 9 years old, have been operated on for an echinococcosis cyst of the lung, by a thoracoscopic procedure. It was a vomited cyst in 6 cases, a pyopneumocyst in 1 case, and a jung noncomplicated and univesicular cyst in 3 cases. The surgical procedure is described. We brought into being the operative conditions such it is nowadays an excellent alternative to the classical thoracotomy.

[Ambulatory anesthesia in pediatric surgery]. / L'anesthesie ambulatoire en chirurgie pediatrique.

Child is an ideal patient for day care surgery. So more than 60% of paediatric surgery could benefit by ambulatory surgery. Preoperative visit may select patients for ambulatory surgery. Medical exam may lead to choose pre operative screening. The ideal ambulatory anesthesia is locoregional technic or inhalatory one. Tracheal intubation don't contre indicate ambulatory surgery. Recovery of mental abilities following general anesthesia has not the same significance as in adult. Many studies confirm the safety of paediatric outpatients anesthesia.

[Isolated fetal pyelectasis: pathologic significance and therapeutic implications]. / Les pyélectasies anténatales isolées: signification pathologique et implications thérapeutiques.

We report a retrospective study of nine neonatal observations of antenatal isolated pyelectasis during a period of two years. Pyelectasis associated with other congenital abnormalities and in utero died foetus were excluded. Finding interesting sex, gestational age at diagnosis, echographic aspect, antenatal management and postnatal follow-up were assigned. Foetal kidneys was noted in two cases and an oligoamnios was noted in two other cases. No foetal urinary intervention was assessed. Postnatal exploration revealed a transitional pyelectasis in four cases, an ureteropelvic junction obstruction in four cases and a congenital megauretere in one case. Postnatal renal function was decreased in two cases. Postnatal surgery was assessed in two cases and a spontaneous regression under a sequential treatment occurred in the other three cases. Isolated foetal pyelectasis can have a pathologic significance.This examination permits, in plus, to evaluate the renal prognosis. Antenatal therapeutic implications of interruption of pregnancy or urinary intervention are still not clear and those after birth depend essentially on renal function determined by scintigraphy.

[Etiologic factors of urinary lithiasis in Tunisian children]. / Facteurs étiologiques de la lithiase urinaire de l'enfant en Tunisie.

Fifty-five Tunisian children with urinary stones, between the ages of 8 months and 15 years, underwent morphological and infrared spectrophotometric analysis of their stones. This study provides an approach to the aetiological profile of urinary stones in Tunisian children. The nucleus of the stones was composed of acidic ammonium urate in 48% of cases with a morphology suggestive of phosphorus deficiency associated with a history of diarrhoea. In 24% of cases, the nucleus contained struvite indicating the presence of urinary tract infection by urease-positive bacteria. The main growth factors of urinary stones were hyperoxaluria and urinary tract infection. In 5 cases, the stones were due to a hereditary lithogenic metabolic disease : cystinuria in 1 case and primary hyperoxaluria in 4 cases.

[Barbus callensis valenciennes barbel, 1842 (fish, Teleostei) of the Ichkeul lagoon]. / Le barbeau Barbus callensis valenciennes, 1842 (poisson, téléostéen) de la lagune de l'Ichkeul.

The Ichkeul lagoon is individualized from the other Tunisian lagoons by the presence of Barbus callensis which is a fresh water fish. We studied the morphometric characteristics of this species in order to characterise this fish and to identify its population in the Ichkeul lagoon.

Combination of partial situs inversus, polysplenia and annular pancreas with duodenal obstruction and intestinal malrotation.

Situs inversus is a challenge to the physician, both for the diagnostic and for the therapeutic. A combination of partial situs inversus, annular pancreas and polysplenia with bowel malrotation has been reported in a newborn who presented as duodenal obstruction. Situs inversus is rare especially without heart malformation. All the abnormalities in this combination can be explained on the basis of multiple organ malrotation. It also demonstrates the necessity of meticulous investigation and precise description of the anomaly as far as the management of this case is concerned.

[Pancreatic pseudocyst in children: what is the best therapeutic approach?]. / Les pseudokystes du pancréas chez l'enfant : quelle approche thérapeutique ?

INTRODUCTION: Pancreatic pseudocyst is an uncommon disorder in children and the majority of reported cases are secondary to trauma. AIM: Treatment options range from medical management to different forms of drainage procedure. The aim of this study was to discuss therapeutic strategies. OBSERVATIONS: The authors report herein pancreatic pseudocyst in four children aged 7, 9, 12, and 13 years with non-resolving pancreatic pseudocyst over a 2-year period from January 2006 to July 2008. The etiology of pancreatic pseudocyst was abdominal trauma in two cases and acute pancreatitis in two cases. Ultrasound and computed tomography scans confirmed the diagnosis. Two patients had endoscopic drainage. There were no procedure-related complications, nor was there a recurrence of the cyst. In one case, the pancreatic pseudocyst resolved spontaneously. CONCLUSION: This report suggests that children with non-spontaneously resolving pancreatic pseudocyst can be treated successfully and safely with endoscopic drainage. Surgical treatment remains an important alternative in the therapeutic armamentarium of this affection.

Small bowel obstruction caused by congenital transmesenteric defect.

Transmesenteric hernias are extremely rare. A strangulated hernia through a mesenteric opening is a rare operative finding. Preoperative diagnosis still is difficult in spite of the imaging techniques currently available. The authors describe two cases of paediatric patients presenting with bowel obstruction resulting from a congenital mesenteric hernia. The first patient had a 3-cm wide congenital defect in the ileal mesentery through which the sigmoid colon had herniated. The second patient is a newborn infant who presented with symptoms and radiographic evidence of neonatal occlusion. At surgical exploration, a long segment of the small bowel had herniated in a defect in the ileal mesentery. A brief review of epidemiology and anatomy of transmesenteric hernias is included, along with a discussion of the difficulties in diagnosis and treatment of this condition.

Primary pelvic hydatid cyst with sciatic compression.

Hydatid cysts are endemic in certain regions of the world and particulary in North Africa. They are usually located in the liver, lung, and spleen, though many uncommon locations have been reported. This is the first report of a child with primary pelvic hydatid disease causing a sciatic compression.