Preliminary national report on cystic fibrosis epidemiology in Tunisia: the actual state of affairs.

AIM: To establish a preliminary national report on clinical and genetic features of cystic fibrosis (CF) in Tunisian children as a first measure for a better health care organization. METHODS: All children with CF diagnosed by positive sweat tests between 1996 and 2015 in children's departments of Tunisian university hospitals were included. Data was recorded at diagnosis and during the follow-up from patients' medical records. RESULTS: In 12 departments, 123 CF children were collected. The median age at diagnosis was 5 months with a median diagnosis delay of 3 months. CF was revealed mostly by recurrent respiratory tract infections (69.9%), denutrition (55.2%), and/or chronic diarrhea (41.4%). The mean sweat chloride concentration was 110.9mmol/L. At least one mutation was found in 95 cases (77.2%). The most frequent mutations were Phe508del (n=58) and E1104X (n=15). Fifty-five patients had a Pseudomonas Aeruginosa chronic colonization at a median age of 30 months. Cirrhosis and diabetes appeared at a mean age of 5.5 and 12.5 years respectively in 4 patients each. Sixty-two patients died at a median age of 8 months. Phe508del mutation and hypotrophy were associated with death (p=0.002 and p<0.001, respectively). CONCLUSION: CF is life-shortening in Tunisia. Setting-up appropriate management is urgent.

A Novel Mutation c.153 C>A in a Tunisian Girl With Wolman Disease and Unusual Presentation: Hemophagocytic Lymphohistiocytosis.

Wolman disease is an ultrarare lysosomal storage disease caused by a mutation in the LIPA gene. The clinical features of Wolman disease include early onset of vomiting, diarrhea, failure to thrive, hepatosplenomegaly, and bilateral adrenal calcification. We report the case of a 3-month-old infant who presented clinical features of hemophagocytic lymphohistiocytosis. Genetic sequence analysis of the LIPA gene revealed homozygous mutation c.153 C>A (p.Tyr51*). The parents were heterozygous for this mutation. Prenatal diagnosis has been carried out in the next pregnancy. To our knowledge, this mutation has never been reported before, and this is an unusual case of secondary hemophagocytic lymphohistiocytosis complicating Wolman disease.

Cystic fibrosis in Tunisian children: a review of 32 children.

BACKGROUND: Cystic fibrosis is rare in Tunisia. Its diagnosis requires experienced specialists. Its prognosis is poor in developing countries. OBJECTIVES: To study the epidemiologic, clinical, genetic features and the therapeutic challenges of cystic fibrosis in Tunisian children. METHODS: Covering a period of 21 years, this retrospective study included all patients with a definite diagnosis of cystic fibrosis from the Pediatrics Department B of The Children's Hospital of Tunis. RESULTS: Data from 32 children (14 boys and 18 girls) were collected. The diagnosis was made during the first year of life in 28 cases. Meconium ileus was found in 5 cases, respiratory manifestations in 22 cases, chronic diarrhea in 19 cases, faltering growth in 17 cases and a pseudo Barter syndrome in 2 cases. The sweat chloride test was positive in all cases. The most frequent mutation was F508del (56% of cases). Respiratory complications marked the outcome. Among our 32 patients, 15 patients (50%) died at an average age of 5 years and 3 months, mainly due to respiratory failure. The mean age of the surviving patients was 5 years. CONCLUSION: Cystic fibrosis prognosis is poor in our series compared to developed countries due to the longer diagnostic delay and the limited therapeutic options.

Pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis in a child with 711+G>T/IVS8-5T mutation: a new face of an old disease.

Pseudo-Bartter syndrome (PBS) describes an uncommon complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. PBS as the sole manifestation of cystic fibrosis in children is extremely rare and has never been described in patients carrying 5T variant. We report a clinical, biochemical and genetic study of a four year-old boy presenting a pseudo-Bartter syndrome as the sole manifestation of cystic fibrosis. All 27 exons and the flanking intron regions of the CFTR gene were analysed by PCR and direct sequencing. Direct sequencing was also used to analyse TGmTn and M470V polymorphisms in the patient and his parents. Two sweat tests were abnormal with elevated chloride levels at 78 and 88 mmol/L. DNA sequencing revealed a heterozygous mutation 711+1 G>T and an IVS8-T5 allele. The mutation 711+1 G>T is in trans with the IVS8-T5-TG11 allele and the child carried M470/V470 genotype. To the best of our knowledge, the genotype 711+1 G>T /IVS8-5T found in our patient is described for the first time. The role of TG11-5T-V470 allele in cases of cystic fibrosis with PB syndrome remains to be determined.

Flexible bronchoscopy contribution in the approach of diagnosis and treatment of children's respiratory diseases: the experience of a unique pediatric unit in Tunisia.

OBJECTIVE: Our study aimed at assessing the role of flexible bronchoscopy (FB) in improving diagnosis and management of children's respiratory conditions in the pediatric unit of FB, newly created and unique in Tunisia. METHODS: Retrospective study including all the FB achieved in our pediatric unit from 2009 to 2014. RESULTS: We performed 365 FB in 333 patients aged 46 months on average (1 month - 15 years), often under conscious anesthesia (81.6%). FB was performed for diagnostic purposes in 341 cases and for therapeutic purposes in 24 cases. Eight anatomical abnormalities were revealed in 22 patients. An intraluminal bronchial obstruction was found in 71 FB, mainly due to a foreign body (n=36). A vascular anomaly was responsible for nine cases out of 17 extraluminal obstructions. Airways malacia was observed in 60 FB. Bronchoalveolar lavage was performed in 196 cases. It was determinant in 43.9% of the cases. FB was of great diagnostic value in 74.8% of the cases. It influenced the management of the patients in 58% of the cases. The FB for therapeutic purposes was beneficial in all cases. Few complications occurred (5.5%). CONCLUSION: FB is a safe tool providing precious diagnostic and/or therapeutic help for the clinician.

Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.

Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a ß-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect.

Mediastina Tuberculosis mass in a three-month-old boy.

BACKGROUND: Mediastinal mass of tuberculous origin is exceedingly rare in infant. AIM: to report an exceedingly rare case of mediastinal mass of tuberculous origin. CASE REPORT: We report a three-month-old boy who presented a one month history of wheezing and persistent pneumopathy. Radiological investigations showed a large posterior mediastinal mass which infiltrates lungs. Thoracoscopic biopsy showed caseous necrosis with granuloma suggestive of tuberculosis. The outcome was favourable with antituberculous chemotherapy. CONCLUSION: Mediatinal mass of tuberculous origin should considered in differential diagnosis of mediastinal masses in children; be suggested in mediastinal mass in children.

Congenital salivary gland anlage tumor of the nasopharynx.

Nasal and upper respiratory tract obstruction in the neonatal period can result from a variety of conditions, and may be present with variable symptoms. Salivary gland anlage tumor, also referred as congenital pleomorphic adenoma, is a very rare benign congenital tumor of the nasopharynx, which may produce nasal obstruction and other associated, nonspecific symptoms. We report a case of congenital salivary gland anlage tumor causing a severe neonatal respiratory distress with pulmonary hypertension. The tumor was removed and the outcome was favourable without recurrence at five years of the follow up.

Central system nervous tuberculosis in infants.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

Giant condyloma acuminatum in an infant.

We report a 10-month-old boy who presented with a giant perianal condyloma acuminatum, and a similar lesion on the neck. These lesions were treated by surgical excision with satisfactory results. This size, extent, and early age of appearance make this case highly unusual.

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.

Megalencephalic leukoencephalopathy with subcortical cysts in a Tunisian boy.

Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive cerebral white-matter disorder in children. Megalencephalic leukoencephalopathy with subcortical cysts is caused by mutation in the megalencephalic leukoencephalopathy with subcortical cysts gene 1. The authors report a case of a 2-year-old Tunisian boy who had presented seizure following minor head trauma. He had megalencephaly, cerebellar ataxia, and mild pyramidal signs at physical examination. Magnetic resonance imaging showed extensive white-matter signal changes involving the corpus callosum and temporal subcortical cysts consistent with megalencephalic leukoencephalopathy with subcortical cysts. The molecular genetic study of the megalencephalic leukoencephalopathy with subcortical cysts gene 1 identified a homozygous mutation C46fsX57 in the patient. The mutation was found to be heterozygous in the parents. To the best of the authors' knowledge, this mutation has never been reported.

Pyelonephritis xanthogranulomatous in childhood: case report and literature review.

BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is a specific form of chronic inflammatory kidney disease rarely seen in children. The Symptoms are often vague and non-specific AIM: the aim of this paper is to return the particularities of imaging features in xanthogranulomatous pyelonephritis, insisting on differential diagnosis with renal tumors, especially in case of no renal stone or tract obstruction evidence. CASE: We report a case of xanthogranulomatous pyelonephritis in a 2-year-old boy involving the lower renal pole which demonstrates the diagnostic difficulties encountered in this disease CONCLUSION: Xanthogranulomatous pyelonephritis is a rare condition in children and should be included in the differential diagnosis of a child presenting a renal mass.

[Infectious diarrhoea in children under five years]. / Les gastroentérites aigues chez les enfants de moins de 5 ans.

AIM: to determine the prevalence of rotavirus in acute diarrhea among children under 5 years and to describe the epidemiology, clinical trials of rotavirus diarrhea and compare them with those of other gastroenteritis. METHODS: A Prospective study during 1 year (1 January 2007-31 December 2007) was conducted in the department of Pediatrics B of the Children's Hospital of Tunis. 117 children aged under than 5 years and admitted for acute community gastroenteritis were included in the study. A search of rotavirus in the stool, collected within 48 hours of admission, was performed by a rapid detection of viral antigens: proteins specific RV group A (VP6 protein of the capsid) using enzyme immunoassay technique: sandwich ELISA (IDEIA Rotavirus Dako). RESULTS: Rotavirus diarrhea accounted for 25% of acute gastroenteritis. The average age of rotavirus gastroenteritis was 11 months +/- 1.78. We have noted a male predominance with a sex ratio of 1.2. The seasonal distribution of rotavirus gastroenteritis showed three peaks of incidence (January, May and July). The respiratory signs were more frequently found in rotavirus gastroenteritis group. Rotavirus gastroenteritis had a higher severity score compared with other gastroenteritis (8.44 vs 6.75 P = 0.01). The duration of hospitalization was longer in rotavirus group with a difference close to significance p = 0.07. CONCLUSION: The seasonal distribution of rotavirus gastroenteritis has three peaks of incidence. The gastroenteritis Rotavirus affects very young infants and has more severe symptoms than other gastroenteritis and is significantly associated with respiratory signs.

Atypical teratoid/rhabdoid tumor of the spine in a 4-year-old girl.

Primary spinal atypical teratoid/rhabdoid tumor is extremely rare. The authors present a case of atypical teratoid/rhabdoid tumor occurring in a 4-year-old girl. Magnetic resonance imaging The authors showed an intramedullary mass extending from the bulbomedullary junction to T1 with leptomeningeal dissemination. The patient died 2 weeks after diagnosis.

Fanconi anemia complicated by neutropenic enterocolitis.

BACKGROUND: Neutropenic enterocolitis (NEC) also known as typhlitis is an acute, life-threatening inflammation of the small and large bowel often seen in patients with leukaemia undergoing cytotoxic chemotherapy: occasionally this syndrome could present in other immunocompromised patients. AIM: To report an unusual case of Fanconi anemia complicated by neutropenic enterocolitis. CASE REPORT: We report a case of a 13-year-old boy affected by Fanconi anemia with severe neutropenia and who presented neutropenic enterocolitis. Abdominal ultrasonography showed thickening of cecum and ascending colon of 1.18cm. The outcome was favourable with medical management. CONCLUSION: Neutropenic enterocolitis in Fanconi anemia is a rare and a severe illness: however, the outcome is improved with early management.