Molecular investigation of distal renal tubular acidosis in Tunisia, evidence for founder mutations.

BACKGROUND: Distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H+ ions in the intercalated cells of the collecting duct. Both autosomal dominant and recessive forms have been described; the latter is also associated with sensorineural hearing loss. METHODS: Twenty-two Tunisian families were analyzed for mutations in the ATP6V1B1 and ATP6V0A4 genes by direct sequencing. Dating of the founder mutations was performed. RESULTS: Two founder mutations in the ATP6V1B1 gene were found in 16/27 dRTA cases. The p.Ile386Hisfs*56 founder mutation was estimated to be older than 2400 years and no correlations were found with deafness. For the remaining patients, two mutations in the ATP6V0A4 gene, one of them being novel, were found in three Tunisian cases. The presence of a heterozygous missense mutation p.T30I, of the ATP6V1B1 gene, was identified in six patients, while no mutations of the second gene were detected. No deleterious mutations of either ATP6V1B1 or ATP6V0A were found for the two probands. CONCLUSION: Our study gives evidence of phenotypic and genotypic heterogeneity of dRTA in the Tunisian population. Five different mutations were found, two of them were due to a founder effect, and screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA.

Hemolytic anemia and progressive neurologic impairment: think about triosephosphate isomerase deficiency.

We have reported the first Tunisian case of triosephosphate isomerase (TPI) deficiency in a 2-year-old girl. She was the first child of a nonconsanguineous couple. The disease included a neonatal onset of chronic hemolytic anemia, recurrent low-respiratory infections then progressive neurological involvement. The diagnosis was made after her death from the TPI values of her parents who exhibited intermediate enzyme deficiency. Molecular study of TPI genes showed that the father and the mother are heterozygous for Glu105Asp mutation. Pediatricians must be alert to the differential diagnosis in patients having hemolytic anemia and other concomitant manifestations.

Multiple congenital anomalies/mental retardation syndrome with multiple circumferential skin creases: a new syndrome?

We describe a combination of multiple congenital anomalies, a severe psychomotor retardation and seizures in a 9-year-old Tunisian boy with circumferential ringed skin creases. He had symmetrical circumferential skin creases on arms, legs, and penis. Craniofacial anomalies included: an elongated face, tight forehead, hypertelorism, bilateral epicanthic folds, upslanting palpebral fissures, microphthalmia, convergent strabismus, wide nasal bridge, aberrant teeth, dental caries, and low-set posteriorly rotated ears with overfolded thick helices. He had also ureterocele, hypospadias, and others anomalies. The magnetic resonance imaging of the brain showed hypoplastic vermis, hypoplastic corpus callosum, and dilatation of ventricles. Chromosomal analysis revealed a normal male karyotype with 46,XY. Skin biopsy was normal. To the best of our knowledge, this combination of anomalies has not been reported and this case may be a unique syndrome.

Evaluation of a model for efficient screening of tuberculosis contact subjects.

RATIONALE: Contact tracing is an important component of tuberculosis (TB) control programs. Standardization of contact investigation protocols can make them more efficient. OBJECTIVES: To develop a model to select contact subjects for screening. METHODS: We prospectively collected standardized data on 325 TB index cases and their 2,009 contacts. Factors that independently influenced the risk of TB infection were included in the model, which was then validated in a second prospective cohort of 88 cases of TB and their 618 contacts. MEASUREMENTS AND MAIN RESULTS: A total of eight independent risk factors were identified (odds ratio; 95% confidence interval): age, with three subgroups: 6-14 years (3.6; 1.6-8.0); 15-29 years (3.7; 1.8-7.7); > or =30 years (4.1; 2.0-8.5); cavitation on the index case's chest radiograph (1.6; 1.1-2.2); an index case sputum smear with 100 or more acid-fast bacilli per field (1.8; 1.2-2.8); household contact at night (2.1; 1.3-3.2); first-degree family relationship with the index case (2.1; 1.3-3.3); active smoking by the contact (1.6; 1.1-2.4); free health care (2.0; 1.2-3.2); and birth in a country with TB incidence rate higher than 25 of 100,000 (2.2; 1.5-3.2). Predictive probabilities were chosen to ensure false-negative rates lower than estimated TB infection background. The number of contacts to be investigated was reduced by 26% while maintaining a false-negative rate of 8%. CONCLUSIONS: This study provides a standardized contact screening model which reduces resources required without negatively affecting disease control.

[Upper gastrointestinal endoscopy in neonates--experience of pediatric gastroenterology unit]. / L'oesogastroduodenoscopie neonatale l'experience d'une unite de gastroenterologie pediatrique.

UNLABELLED: The aim of our study was to assess the frequency of the different lesions occurring as well as to precise indications of upper gastrointestinal endoscopy in neonates. METHOD: We have achieved a retrospective study about 128 neonatal gastrointestinal endoscopies. Three groups were constituted according to macroscopic findings: Group I: normal aspect (n=11); Group II: isolated esophagitis (n=19); Group III: esogastritis or gastroduodenitis or esogastroduodenitis (n=92). RESULTS: The neonates undergoing endoscopy for malaise were more frequent in group I than in group II and III, respectively 36.5% versus 15.8% and 9.8% (P = 0.04). Digestive hemorrhage (hematemesis and/or melena) was more frequent in group III than in group II and I, respectively 90.2% versus 78.9% and 63.6% (P = 0.03). Digestive hemorrhage was in our study the main indication of upper gastrointestinal endoscopy in neonates (85.9%) which showed a macroscopic lesion in 93.5% of cases. CONCLUSION: Hematemesis and suspicion of esophagitis are good indications for upper gastrointestinal endoscopy in neonates.

[Hyperlipidaemia associated to inaugurated diabetic ketoacidosis]. / Hyperlipemie associee a une acidocetose diabetique inaugurale.

Severe hyperlipidaemia in presenting diabetic ketoacidosis was rarely reported in child. We report the case of a three-year-old girl with presenting diabetic ketoacidosis. Family history was negative for hyperlipidaemia. Serum was creamy pink in gross appearance. The child has a hyperlipidaemia with serum triglycerides 18.5 mmol/l and serum cholesterol 13.8 mmol/l. The hyperlipidaemia disappeared with insulin therapy within seven days. We study the clinical, laboratory, pathogenic and evolution features of this uncommon trouble in diabetic 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.