Novel and recurrent AID mutations underlie prevalent autosomal recessive form of HIGM in consanguineous patients.

Immunoglobulin class switch recombination deficiencies (Ig-CSR-D) are characterized by normal or elevated serum IgM level and absence of IgG, IgA, and IgE. Most reported cases are due to X-linked CD40L deficiency. Activation-induced cytidine deaminase deficiency is the most frequent autosomal recessive form, whereas CD40 deficiency is more rare. Herein, we present the first North African study on hyper IgM (HIGM) syndrome including 16 Tunisian patients. Phenotypic and genetic studies allowed us to determine their molecular basis. Three CD40LG mutations have been identified including two novels (c.348_351dup and c.782_*2del) and one already reported mutation (g.6182G>A). No mutation has been found in another patient despite the lack of CD40L expression. Interestingly, three AICDA mutations have been identified in 11 patients. Two mutations were novel (c.91T>C and c.389A>C found in one and five patients respectively), and one previously reported splicing mutation (c.156+1T>G) was found in five patients. Only one CD40-deficient patient, bearing a novel mutation (c.109T>G), has been identified. Thus, unlike previous reports, AID deficiency is the most frequent underlying molecular basis (68%) of Ig-CSR-D in Tunisian patients. This finding and the presence of specific recurrent mutations are probably due to the critical role played by inbreeding in North African populations.

[Diagnosis and management of cow's protein milk allergy in infant]. / Diagnostic et prise en charge de l'allergie aux protéines de lait de vache chez le nourrison.

BACKGROUND: Cow's milk protein allergy (CMPA) can be responsible of a variety of symptoms and can be caused by IgE or non-IgEmediated reactions. The remaining questions concern the diagnosis (what are the most suggestive clinical manifestations, the laboratory evaluations which play a supporting role, and the management of CMPA in breast fed infants and formula-fed infants. METHODS: Review of the pub med, science direct, Cochrane library, using the key words cow's milk protein allergy, guideline, and child. Evidence was levelled A, B, C. RESULTS: No symptom is pathognomonic. A thorough history and careful clinical examination are necessary to suspect the disease. Skin prick tests, and serum specific IgE are only indicative of sensitivation to CMP. A double-blind placebo-controlled challenge is considered the gold standard in diagnosis, but in practice only an open challenge is performed. The patient with suspected pathology will follow a cow's milk free diet for 2-4 weeks. Formula-fed infants get an extensively hydrolyzed formula .If the allergy is present, clinical manifestations will disappear. If symptoms do not improve, an amino acid based formula should be considered. In severe Cow's milk protein allergy with life-threatening symptoms, an amino-acid formula is recommended. The infant should be maintained on an elimination diet until the infant is between 9-12 months or at least for 6 months. The overall natural evolution of the disease is favorable with most patients achieving tolerance to milk by the age of five years. CONCLUSION: The importance of defined diagnostic criteria needs to be emphasized. It precludes infants from an unnecessary diet and avoids delay in diagnosis, which can lead to malnutrition.

Pneumococcal infection and hemolytic uremic syndrome.

BACKGROUND: Hemolytic uremic syndrome, one of the common causes of acute renal failure in children, is characterized by the triad of microangiopathy, haemolytic anemia, thrombocytopenia and acute renal failure. The diarrhoea-associated Hemolytic uremic syndrome is usually termed as a typical Hemolytic uremic syndrome. Streptococcus pneumoniae is an uncommon etiological pathogen for inducing Hemolytic uremic syndrome, and Streptococcus pneumoniae associated Hemolytic uremic syndrome is also termed as atypical hemolytic uremic syndrome. AIM: to report two pediatric cases of invasive S pneumoniae complicated with hemolytic uremic syndrome HUS. CASE REPORT: The first patient presented with pneumococcal pneumonia and empyema and the second patient presented with pneumococcal pneumonia and meningitis. The two patients were under one year of age and required peritoneal dialysis with improvement of renal function in one; the other died. CONCLUSION: Pneumococcal invasive disease may be a cause of severe HUS, so a high index of suspicion is mandatory to prompt appropriate diagnosis and management.

[Chronic gastritis in children]. / Les gastrites chroniques chez l'enfant.

BACKGROUND: Active gastritis, atrophic gastritis (AG) and intestinal metaplasia are lesions associated with Helicobacter pylori (H. pylori) infection in adults. AIM: To assess the prevalence of chronic gastritis, its histological characteristics and clinical features in children. METHODS: 345 children (M/F: 151/194, mean age: 8.6 +/- 3.7 years; range: 1-18 years) were enrolled, referred for upper gastrointestinal endoscopy (UGI endo) with clinical manifestations of gastritis, i.e., recurrent abdominal pain (n = 232, 67.2%), upper gastrointestinal bleeding (n = 59, 17.1%) and miscellaneous (n = 53, 15.3%). Four perendoscopic gastric biopsy specimens (antrum: 2, fundus: 2) were taken. Biopsies were assessed and graded according to the updated Sydney system. H. pylori infection was considered if 2 out 3 tests were positive (culture, histology and rapid urease test), whereas 3 concordant negative results identified H. pylori negative children. RESULTS: H. pylori infection and chronic gastritis were detected in 215/345 (62.3%) (M/F: 104/117, sex ratio M/F = 0.89) and 221/345 (64.05%) children, respectively. Recurrent abdominal pain (n = 149, 67.4%) was the main clinical features of chronic gastritis followed by vomiting (n = 43, 19.5%) and upper gastrointestinal bleeding (n = 41, 18.6%). Any clinical features were however found to be specific. UGI endo showed; nodular gastritis (n = 90, 40.72%), congestive gastritis (n = 84, 38%), gastric ulcer (n = 9), bulbar ulcer (n = 5) and normal (n = 47, 21.2%). Chronic gastritis was active in 115 cases (52%) and was significantly associated with nodular gastritis (p < 0.05). Thirty two chronic gastritis (14.4%) exhibited AG (M/F: 16/16, mean age: 9.4 +/- 3.4 years) and 30/32 (93.7%) were H. pylori positive. AG was significantly associated with H. pylori infection (p < 0.0001) and nodular gastritis (p < 0.005). Active, follicular and AG were significantly associated with H. pylori infection (p < 0.00001). Three patients exhibited intestinal metaplasia. CONCLUSION: Chronic gastritis is frequent in children. Any clinical features were found to be specific. It significantly associated H. pylori infection and nodular gastritis. Atrophic gastritis was found in 14.5% of children.

[Congenital hepatic fibrosis in children. Report of 9 cases and review of the literature]. / Fibrose hepatique congenitale chez l'enfant. A propos de 9 cas et revue de la litterature.

Congenital hepatic fibrosis is a recessive autosomic disease with two major risks: gastrointestinal haemorrhage caused by portal hypertension and cholangitis related to bacterial infection of dilated intrahepatic bile ducts.. The aim of our study is to define epidemiological features, the presenting symptoms, the diagnosis, the evolution and the management of this disease. Between January 1990 and December 2000, we reported the cases of nine children with this disease at children hospital of Tunis. Three were male and six female. The mild age was three years and six months. Consanguinity was present in five cases and similar cases were found in six cases. The FHC was revealed by portal hypertension in five cases, angiocholitis in one case and by portal hypertension and angiocholitis in three cases. Liver biopsy was done in seven children. Ultrasound examination of the liver and kidney revealed caroli syndrome in five cases and polykystose renal in two cases The intravenous pyelography was performed in four cases showing precalicial canalicular ectasia in four cases. Eosophageal endoscopy had shown oesophageal varices in six patients. The follow up had shown that three patients had gastrointestinal bleeding, three had angiocholitis. One patient died with multivisceral failure. The treatment of acute bleeding has needed blood transfusion in four cases. Primary prevention of bleeding was done by endoscopic sclerosis alone in one case and associated to betablokers in two cases. Secondary prevention of varices bleeding was done by sclerotherapic in two cases, by beta blokers alone in one case and by betablokers associated to elastic ligation of oesophageal varices in one case.

[Esophagogastroduodenitis in the newborn. Report of 90 cases]. / Les oesogastroduodenites du nouveau-ne. Etude de 90 observations.

Oesophagogastroduodenitis (OGD) is a frequent situation in the newborn and run a benign course. Ninety cases of OGD were studied. Diagnosis was established by endoscopy. Presenting symptoms are dominated by gastrointestinal bleeding (70 percent of cases). Oesophagitis and/or gastritis were observed in all cases, associated with duodenitis in 34.5 percent of cases. Evolution was good with complete recovery of the symptoms and healing of mucosal lesions in 74.4 percent of controlled patients. Pathogenesis of neonatal OGD remains undetermined.

[Contribution of clinical, biological and radiological parameters in the diagnosis of urinary infection localization]. / Apport des parametres cliniques biologiques et radiologiques dans le diagnostic de localisation de l'infection urinaire.

Urinary infection was a problem in pediatrics. Currently the diagnosis is easy but it is hard to diagnosis the localisation of the infection. We have to go fast and precisely to treat correctly this infection and diminich the possibility of developing renal scars. Dimercaptosuccinic acid (DMSA) scintigraphy is a reference exam for detection acute renal lesions. We have realised a prospective study in 29 children presenting urinary tract infection. In whom a DMSA scintigraphy is realised between the one day and 30 days after the infection. We study the sensibility ans the specificity of clinical, biological and radiological parameter for the diagnosis of localisation of the infection. The better parameter of sensibility of upper urinary tract infection is of fever, and the better parameter of specificity is the association of fever, echo Doppler renal and VS.