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Candida albicans colonizes the respiratory tract of patients with Cystic Fibrosis (CF). It competes with CF-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, and contributes to disease severity. We serially recovered 160 C. albicans clinical isolates over a period of 30 months from the sputum of 23 pediatric and 2 adult antifungal-naive CF patients at Children’s Hospital Tunis and characterized the genotype and phenotype of a subset of strains using multilocus sequence typing (MLST) and growth assays on multiple stress-, filamentous growth- and biofilm-inducing media. Out of 16 patients regularly sampled for at least 9 months, 8 and 4 were chronically and transiently colonized with C. albicans, respectively. MLST analyses of 56 strains originating from 15 patients indicated that each patient was colonized with a single strain, while 8 patients (53%) carried isolates from clade 4 known to be enriched with strains from Middle East-Africa. A subset of these isolates with the same sequence type and colonizing 3 unrelated patients displayed altered susceptibility to cell wall-perturbing agents, suggesting changes in cell wall structure/function during growth in the CF lung. We also observed differential ability to filament and/or form biofilms in a set of identical isolates from clade 10 sampled over a period of 9 months in a pediatric CF patient, suggesting alterations in phenotypes associated with virulence. Our findings will rely on future whole-genome sequencing analyses to identify polymorphisms that could explain the emergence of new traits in C. albicans strains thriving in the CF host environment.

This study aimed to analyse the frequency of genes encoding virulence factors and to characterize resistance profiles of Staphylococcus aureus isolated from raw milk. In total, 47 and 9 S. aureus isolates were recovered from 150 and 100 raw bovine and ovine milk samples, respectively, in Tunisia. The majority of isolates was resistant to penicillin, and no methicillin-resistant S. aureus was detected. Eighteen and two isolates harboured etd and eta genes respectively. Sixteen enterotoxin-encoding genes were detected (n, %): sed (25, 44·6%), sec (16, 28·6%), sei (16, 28·6%), seh (13, 23·2%), seln (13, 23·2%), sell (10, 17·8%), seg (9, 16%), selu (8, 14·3%), selq (7, 12·5%), selo (7, 12·5%), selm (7, 12·5%), seb (7, 12·5%), sea (6, 10·7%), selk (3, 5·4%), ser (1, 1·8%) and selp (1, 1·8%). Ten isolates carried the tsst1 gene. All isolates carried the haemolysin toxin (hla, hld and hlg). The immune evasion cluster system-type B was predominant (20 isolates) followed by C (3 isolates), A and E (1 isolate each). The occurrence of enterotoxigenic S. aureus in raw milk constitutes a potential risk for human health. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper describes the characteristics of Staphylococcus aureus isolated from raw milk samples from healthy cows and ewes collected from small family farms in Tunisia. Fifty-six strains were analysed by determining their antibiotic susceptibility and genes encoding antibiotic resistance and virulence factors. Methicillin-resistant strains were not detected, and overall low level of antimicrobial resistance was reported. However, our strains harboured several genes encoding virulence factors and 87·5% of them carried at least one gene encoding for enterotoxins showing a high risk of spread of food-borne diseases.

Objectives This study aimed to screen for and characterise methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in nasal swabs and milk from healthy cows from different regions in Tunisia. Methods A total of 141 Staphylococcus spp. isolates were recovered from milk and nasal samples of cows. S. aureus isolates were further characterised by determining their antimicrobial susceptibilities, genes encoding antimicrobial resistance and virulence factors, biofilm production, agr type and PFGE. spa and SCCmec typing and MLST were also performed for the MRSA isolate. Results Twenty-seven isolates (19.1%) were identified as S. aureus, of which 26 were MSSA and 1 was MRSA. The MSSA isolates were resistant to penicillin (73.1%), fusidic acid (61.5%), clindamycin (34.6%) and erythromycin (34.6%). The MRSA isolate, from a milk sample, was resistant to cefoxitin, penicillin, fusidic acid, amikacin and clindamycin. Twenty-five isolates (92.6%) had at least one enterotoxin gene. Only four isolates (14.8%) were positive for the tsst-1 gene. Genes encoding the exfoliative toxins D and A were detected in 9 (33.3%) and 6 (22.2%) isolates, respectively. The single MRSA isolate and 22 MSSA isolates were biofilm-producers on Congo red agar plates. Twelve pulsotypes were identified amongst 25 MSSA isolates revealing the clonal diversity of these isolates; however, one MSSA isolate was identified as CC398. The MRSA isolate was PVL-negative and was typed as ST97-t267-agrI-SCCmecV. Conclusion Contamination of milk with S. aureus, especially enterotoxin- and TSST-1-positive strains, poses a potential public-health threat. This is the first report of MRSA of bovine origin in Tunisia.

Objectives The aim of this study was to characterize 32 MRSA isolates recovered from wound specimens of patients in a Hospital in Tripoli, Libya, during 2013. Methods MRSA isolates were characterized by determining their antibiotic susceptibilities, genes encoding antibiotic resistance and virulence factors, the SCCmec class, agr type, spa typing, PFGE and MLST. Results PFGE and MLST revealed that all isolates were clonal and belonged to the Clonal Complex 5 (CC5). They harboured the SCCmecV and the agrII and the spa type was t6065. The majority of isolates were resistant to cefoxitin (32, 100%), penicillin (32, 100%), ampicillin (32, 100%), enrofloxacin (32, 100%), ciprofloxacin (32, 100%), fusidic acid (32, 100%), gentamicin (32, 100%), kanamycin (32, 100%), trimethoprim (32, 100%), and erythromycin (30, 93.7%). The main genes encoding antibiotic resistance were: blaZ (31, 96.8%), ermC (30, 93.7%), aph(3')-III a (3, 9.4%), aac6-aph2 (32, 100%), InuA (3, 9.4%), tetM (3, 9.4%), tetL (3, 9.4%), dfrG (28, 87.5%), fusC (32, 100%). All isolates were PVL negative; however, exfoliative-encoding genes (eta: 25) and enterotxin genes (seb: 32, seo: 32, sei: 32, ser: 32, seu: 32, seg: 32, sej: 32, sed: 31, sen: 29, seh: 26, sec: 26, sea: 6, sek: 5), haemolysin (hla (32), hld (32), hlg (32)) and immune evasion cluster proteins (scn: 32, sak: 32) were relevant. Conclusion To the best of our knowledge this is the first report of a specific clonal spread of a multi-drug resistant MRSA-CC5- SCCmecV in a Libyan Hospital.

To report clinical presentation and etiologic investigation findings during pediatric noncerebral thromboembolism.Retrospective study of cases of vascular non cerebral thromboses admitted in Medicine infantile A Department of the Children's Hospital of Tunis over 08 years.We confirmed 14 cases of non cerebral vascular thromboses. So that these accidents constitute 0,26 ‰ of the overall etiologies of hospitalizations in the Department. The mean age of our patients was 56±41 months [25 days-12 1/2 years]. The sex ratio was 1.8. The vascular incident was venous in 2/3 of cases. The clinical presentation was mainly painful swelling in four cases, abrupt dyspnea and hematemesis in three cases each and the incident was locally asymptomatic in four cases. Thromboses locations included deep vein thrombosis of limbs (n=6), vena cava thrombosis (n=1), portal thrombosis (n=4) and pulmonary embolism (n=3). The promoting factors identified were: tumors in seven cases, thrombophilias and catheterization in four cases each, trauma, surgery and Behçet disease in one case each. Eleven patients received anticoagulant treatment including unfractioned heparin in three cases and low molecular weight heparin in the other cases. No one died while four patients developed sequelae.Vascular thromboses are rare in children. They are mostly venous and diagnosed in ill children especially those having central venous catheters. Outcome of pediatric thromboembolism depends on efficient anticoagulation therapy which is well tolerated by children.

Introduction Depuis decembre 2019, la propagation du nouveau coronavirus (le SARS-CoV-2) constitue le premier souci mondial. Etant un virus a tropisme respiratoire, l’asthme constitue-t-il un facteur de mauvais pronostic ? A l’heure actuelle on predispose de peu de donnees pouvant etablir cette relation. L’objectif de notre travail est de faire le point a travers une serie de 40 malades sur la presentation clinique et evolutive des enfants asthmatiques atteints de la COVID 19. Methodes Etude retrospective incluant les enfants hospitalises pour infection par le SARC-Cov2, a l’hopital d’enfants de Tunis, durant la periode allant du 1 octobre au 31 decembre 2021. Resultats Nous avons collige 40 cas de COVID 19 dont 24 garcons. L’âge moyen etait de 5 ans avec des extremes allant de 25 jours a 12 ans. Huit parmi nos malades etaient suivis pour asthme sous traitement de fond. Ils etaient hospitalises pour une crise d’asthme induite par le SARS-Cov2 (une severe, six moderees et une legere). Cinq patients ont eu recours a une oxygenotherapie (4 par lunettes nasales simples et 1 par lunettes nasales a haut debit) avec une duree moyenne de 3 jours. Un seul malade etait hospitalise en reanimation pendant 24 h. L’evolution etait favorable pour tous les patients avec une duree d’hospitalisation moyenne de 3,5 jours. Parmi les enfants non asthmatiques (n = 32), 4 etaient hospitalises pour une crise d’asthme (une severe et 3 moderees). Une oxygenotherapie par lunettes nasales simples etait indiquee dans un cas pendant 48 h. La duree moyenne d’hospitalisation etait de 3 jours. Discussion Les dernieres etudes demontrent que l’asthme n’est pas un facteur de risque pour la COVID-19 severe. Les patients[p1] asthmatiques semblent etre proteges contre les formes graves du SARS-COV2 du fait de leur plus grande prudence vis-a-vis des mesures de distanciation sociale et de leur traitement de fond. Conclusion L’asthme ne semble pas etre un facteur predictif d’atteinte severe par le SARS-Cov2. Toutefois, il faut rester vigilant avec tous les enfants suivis pour asthme et assurer un bon controle afin de limiter le risque d’exacerbation de la maladie.

International audience; Chronic granulomatous disease (CGD) is the prototypic functional neutrophil disorder caused by genetic defects in one of the five genes encoding the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits of phagocytes. Mutations causing the most prevalent form of CGD in western populations are located in the X-linked-CYBB gene. The four remaining autosomal recessive (AR) forms collectively account for one-third of CGD cases. We investigated the clinical and molecular features of eleven patients with CGD from 6 consanguineous families, originating from contiguous regions in the west of Tunisia. The patients' clinical phenotype is characterized by a high incidence of mycobacterial infections. Five out of the eleven patients died despite treatment arguing in favor of a severe clinical form of CGD. These findings correlated with the absence of functional p67phox protein as well as the absence of residual reactive oxygen intermediates (ROI) production. Genetic analysis showed the presence, in all patients, of a unique mutation (c.257 + 2T > C) in NCF2 gene predicted to affect RNA splicing. Segregating analysis using nine polymorphic markers overlapping the NCF2 gene revealed a common haplotype spanning 4.1 Mb. The founder event responsible for this mutation was estimated to have arisen approximately 175 years ago. These findings will facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families.

Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents.

Summary Background Bloom syndrome is a rare disease characterized by chromosomal instability and increased risk of developing lymphoma. Observation We report on a case of Bloom syndrome in a 5-year-old boy with Burkitt lymphoma. The diagnosis was suspected by growth retardation, repeated respiratory infections, facial telangiectasia, and a low immunoglobulin level, then confirmed cytogenetically by sister chromatid exchanges. Chemotherapy was poorly tolerated, which required reducing the doses. Unfortunately, it was not sufficient to control the neoplasm and the patient died 14 months after diagnosis. Conclusions Cancers in Bloom syndrome are a challenge since the potentially life-threatening side effects of the chemotherapy may require modifications in standard treatment such as dose reduction, which can compromise the tumor prognosis.

Introduction: Bacterial meningitis is a medical emergency requiring a fast and reliable diagnosis. Molecular methods such as real-time PCR (rt-PCR) offer an attractive alternative. Thus, this study aims to establish multiplex rt-PCRs detecting N. meningitidis, S. pneumoniae and H. influenzae b from cerebrospinal fluid in Tunisian children beyond neonatal age. Methodology: Using bioinformatic tools and experimentation, we validated the specificity and optimal criteria of PCRs for primers and probes of plyA (S. pneumoniae), ctrA and sodC (N. meningitidis) and bexA genes (H. influenzae b). We performed one multiplex RT-PCR for detection of S. pneumoniae and N. meningitidis targeting plyA and ctrA, sodC genes respectively, simultaneously with a singleplex RT-PCR for H. influenzae b. The sensitivity and specificity of our methods were assessed. Then, we tested our methods for 122 CSF samples collected from suspected meningitis cases between 2014 and 2016 in Bechir Hamza Children’s Hospital of Tunis. Results: Our results have shown the sensitivity of the designed PCRs was up to 10-4 DNA dilution and the specificity was 100%. PCR evaluation has shown 51 positive samples: 38 of pneumococcal cases, 12 meningococcal cases, 1 case of H. influenzae b with 8.57% and 50% of supplementary positive cases rates respectively. Conclusions: Our assay proved to be very sensitive, specific and rapid for bacterial meningitis diagnosis. In the recent context of Hib vaccination, the possibility of detecting S. pneumoniae and N. meningitidis separately constitute an attractive opportunity. Nevertheless, simultaneous detection of Hib remains relevant in specific clinical context and for epidemiologic study.

Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Mutations in PGM3 gene have been recently shown to underlie a new congenital disorder of glycosylation often associated to elevated IgE. Herein, we report twelve PGM3 deficient patients. They belong to three highly consanguineous families, originating from a rural district in the west central Tunisia. The patient's clinical phenotype is characterized by severe respiratory and cutaneous infections as well as developmental delay and severe mental retardation. Fourteen patients died in early infancy before diagnosis supporting the severity of the clinical phenotype. Laboratory findings revealed elevated IgE, CD4 lymphopenia and impaired T cell proliferation in most patients. Genetic analysis showed the presence, of a unique homozygous mutation (p.Glu340del) in PGM3 gene leading to reduced PGM3 abundance. Segregating analysis using fifteen polymorphic markers overlapping PGM3 gene showed that all patients inherited a common homozygous haplotype encompassing 10-Mb on chromosome 6. The founder mutational event was estimated to have occurred approximately 100 years ago. To date, (p.Glu340del) mutation represents the first founder mutation identified in PGM3 gene. These findings will facilitate the development of preventive approaches through genetic counselling and prenatal diagnosis in the affected families.

Major histocompatibility complex class II (MHC-II) expression deficiency is a combined primary immunodeficiency leading to the impairment of the cellular and humoral immune responses. A majority of affected patients belong to consanguineous families particularly from the Maghreb, where a founder effect for a highly frequent mutation (named c.338-25_338del26) in the RFXANK gene was reported. Herein, we report the largest single Maghrebian country series of MHC-II deficient patients.In Tunisia, among 551 PIDs diagnosed from 1993 to 2011, 54 had an MHC-II deficiency. The clinical features and immunological investigations were retrospectively analyzed in 34 children of them belonging to 28 kindred. The genetic study included the c.338-25_338del26 screening by the amplification of the affected region using polymerase chain reaction (PCR) followed by direct sequencing.Consanguinity was present in 22 out of 28 families. Mean age at the first infection was 6.1 months. Chronic diarrhea with failure to thrive and pulmonary infections were the most common manifestations occurring in 26 and 28 patients respectively. The most specific laboratory findings were the defect of MHC-II (HLA-DR) expression in all patients. The c.338-25_338del26 mutation was identified in 25 of them.In Maghrebian settings, pediatricians should definitely consider this diagnosis in the presence of an early onset of severe and recurrent infections of the respiratory and intestinal tracts, particularly protracted diarrhea with a failure to thrive. The founder effect for the c.338-25_338del26 mutation in the RFXANK gene is also confirmed, facilitating prenatal diagnosis as a preventive approach in the Tunisian affected families with severe forms, particularly in the context of limited access to bone marrow transplantation.

Background Extracranial Germ cell tumors (GCT) are a rare and a heterogeneous group of pediatric cancers but highly curable. Aim We aimed to review management, outcome and prognostic factors that influence overall survival (OS) in a pediatric Tunisian oncologic unit. Methods We retrospectively evaluated between January 1998 and December 2012, 33 patients affected by extracranial germ cell tumors and treated according to TGM95 protocol established by the SFOPin a pediatric Tunisian oncologic unit. Results Patients had a mean age of 57 months (ranges: 1 day-13 years). There were 19 girls and 14 boys. Primary sites included 12 sacrococcygeal, 11 ovarian, 6 testicular, 3retro peritoneal and 1 mediastinal site. After a mean follow up of 26.1 months (ranges: 0-96 months), OSat 2 years and 5 years were respectively 82% and 75%. Event-free survival were respectively 79% at 2 years and 74% at 5 years. Various prognostic factors have been studied according to Kaplan-Meier. Univariate analyses identified significant factors which influence strongly OS: the stage (p=0.04), the completeness of surgery (p0.001) and the relapse (p = 0, 0001). A multivariate study showed that only the quality of resection and the clinical stage remained strong significant prognostic factors (p=0,021) for 5-year OS. Conclusion Disease stage, completeness of surgery and relapse have been established as the most powerful prognostic parameter in our analysis. The improvement of survival of patients affected by extracranial germ cell tumors in Tunisia is a real achievement mainly due to the success of salvage treatments.

Background Myoepithelial carcinoma was only recently recognized to occur primarily in soft tissue. Only a small number has been reported in children. Observation We report a rare case of myoepithelial carcinoma of the leg in a 4-month-old boy with a good response to chemotherapy initially. However, he presented secondarily during chemotherapy a local and metastatic progression. Conclusions The rarity of the tumor and unusual age of discovery have prompted us to report this case. Our case suggests that this disease can have an aggressive behavior. This is why we advise a rapid and correct diagnosis followed by an aggressive treatment.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy. More than 200 mutations in the G6PD gene have been described. In Tunisia, the A-African and the B-Mediterranean mutations predominate the mutational spectrum. The purpose of this study was to apply the amplification refractory mutation system (ARMS-PCR) to the identification of Gd A+, Gd A- and Gd B- variants in a cohort of deficient individuals and to establish a phenotype/genotype association. 90 subjects were screened for enzymatic deficiency by spectrophotometric assay. The molecular analyses were performed in a group of 50 unrelated patients. Of the 54 altered chromosomes examined, 60% had the Gd A- mutation, 18% showed the Gd B- mutation and in 20% of cases, no mutations have been identified. The ARMS-PCR showed complete concordance with the endonuclease cleavage reference method and agreed perfectly with previous Tunisian studies where Gd A- and Gd B- were the most encountered. Also, similarities in spectrum mutations with North African and Mediterranean countries suggest gene migration from Africa to Europe through Spain. In conclusion, ARMS has been introduced in this study for common G6PD alleles identification in Tunisia. It gives some advantages compared to the traditional endonuclease digestion method since it is more convenient and timesaving and also offers the possibility to be applied in mass screening surveys.

Resume Objectif Les malformations pulmonaires kystiques (MPK) constituent un groupe d’affections rares caracterisees par un grand polymorphisme clinique et radiologique. Il s’agit ici de rapporter les differents tableaux cliniques realises par les MPK et de discuter les difficultes diagnostiques rencontrees. Patients et methodes Nous avons realise une etude retrospective des observations de MPK diagnostiquees durant une periode de 11 ans (janvier 1994–decembre 2004) dans notre institution. Resultats Trente-trois MPK ont ete diagnostiquees chez 30 enfants (17 garcons et 13 filles) âges au moment du diagnostic de 20 jours a 16 ans. Il s’agit de 17 emphysemes lobaires congenitaux (ELC), sept kystes bronchogeniques (KB), cinq malformations adenomatoides kystiques (MAK) et quatre sequestrations pulmonaires (SP). Trois patients avaient deux malformations associees. L’âge au diagnostic va de deux a 88 mois. Les manifestations revelatrices etaient : une detresse respiratoire ( n = 14, 46,6 %), une dyspnee paroxystique ( n = 6, 20 %), une infection pulmonaire ( n = 8, 26,6 %) compliquee d’hemoptysie dans deux cas, un hemothorax et une decouverte fortuite dans un cas chacun. L’exploration radiologique a conduit au diagnostic dans tous les cas d’ELC et de MAK mais elle etait moins contributive pour la SP et le KB. Vingt-neuf patients ont ete operes : 22 ont necessite une lobectomie, deux une pneumonectomie et huit une kystectomie. L’examen histologique a confirme le diagnostic dans tous les cas et l’a redresse dans quatre cas. L’evolution au bout d’un recul moyen de 24 mois (quatre mois a sept ans) etait favorable chez 26 patients. Trois enfants ont developpe un wheezing episodique et transitoire et un malade est decede dans les suites operatoires d’une infection nosocomiale. Conclusion Les MPK peuvent etre responsables d’un grand polymorphisme clinique et radiologique. Les tableaux cliniques realises dependent du type de la malformation, de sa topographie et de ses complications evolutives.

PubMedID: 25724123 Background Mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency (CID) also classified as autosomal recessive (AR) hyper-IgE syndrome (HIES). Recognizing patients with CID/HIES is of clinical importance because of the difference in prognosis and management. Objectives We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings. Methods Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations. Results DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/µL (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4+ and CD8+ T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations. Conclusions DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures. © 2015 American Academy of Allergy, Asthma & Immunology. National Institutes of Health: R01AI065617 National Institutes of Health: R21AI087627

Infants younger than six months of age are at an increased risk of methemoglobinemia (MTH) (Woolf and Wright, 2004). However, severe toxic MTH with a methemoglobin rate exceeding 60% has been rarely reported in the pediatric literature. The diagnosis may be unrecognized in infants, with a life-threatening condition due to multivisceral tissue hypoxia. We illustrate with the following case the occurrence of a central cyanosis associated to neurological distress and cardiovascular shock, due to a severe MTH in a young infant exposed to nitrites.

Eosinophilic pneumonias are a group of heterogeneous disorders, rarely reported in children. We describe a case of a 12-year-old boy hospitalized for an acute febrile respiratory failure. Chest radiograph showed bilateral diffuse infiltrates. A pulmonary eosinophilic infiltration was confirmed by a major blood eosinophilia at 33,800/mm(3) associated with increased eosinophilic rate (90%) on bronchoalveolar lavage fluid. Outcome improved markedly with mechanical ventilation and corticosteroid therapy. Laboratory screenings for parasitic or allergic disease were negative. Bone marrow smear and medullar caryotype eliminated an acute leukemia. No further visceral eosinophilic injury were found. Acute eosinophilic pneumonia should be included in etiological investigation of patients with acute respiratory distress syndrome (ARDS) even in young subjects.

International audience; Invasive aspergillosis is a life-threatening condition in patients with chronic granulomatous disease (CGD). Skin invasion by Aspergillus occurs most commonly by contiguity to a neighboring cavity. We describe an unusual case of invasive cutaneous aspergillosis presented as a large burgeoning tumor in a 4-year-old girl with CGD who underwent surgical treatment for bifocal osteomyelitis of the left leg. The skin invasion occurred 4 months after a "successful" treatment of invasive pulmonary aspergillosis. Atypical presentation and diagnostic difficulties are discussed. Invasive cutaneous aspergillosis may be polymorphic. The diagnosis should be considered early in the etiological investigation of any suspicious skin lesions in CGD even in uncommon aspects such as burgeoning tumors.

The Bacille Calmette-Guérin vaccination (BCG) contributed widely to reduce tuberculosis incidence in developing countries. The aim of this report was to assess the clinical “spectrum” and outcome of tuberculous meningitis in 16 Bacille Calmette-Guérin–vaccinated Tunisian children. They were 9 boys and 7 girls aged 2 to 168 months (median 72 months ± 65.88). Patients presented mainly with nonspecific symptoms. Neurologic severity was classified as grade I (n = 6) and grade II or III (n = 10). At short-term course, the majority of patients developed serious complications: hydrocephalus (n = 12), seizures (n = 8), tuberculoma (n = 6), and acute respiratory failure (n = 2). Three patients died. Among survivors, 4 patients showed a complete recovery while 9 developed permanent sequelae which were mild (n = 6) to severe (n = 3). Despite the Bacille Calmette-Guérin vaccination, tuberculous meningitis remains a life-threatening condition; vaccinated children have shown common presentation of tuberculous meningitis in terms of severity and poor outcome.

The aim of this report is to determine frequency and clinical characteristics of Congenital lobar emphysema (CLE) at Children's Hospital of Tunis.Cases of CLE managed between January the 1st 1994 until December the 31st 2004 were reviewed.Amongst 31 cases of cystic pulmonary malformations we report 17 CLE. They were 12 males and 5 females. The mean age at diagnosis was 41/2 months (20 days, 22 months). Symptoms were: progressive respiratory distress (n=11) recurrent attacks of dyspnea (n=5); pulmonary infection (n=1). Chest X ray and CT scans showed hyper aeration of the affected lobes. Three patients had two affected lobes. CLE was associated to bronchogenic cyst (n=2) and to congenital cardiac anomalies (n=3). All patients underwent lobectomy. Post operative course was uneventful in 16 children.CLE is an uncommon cause of respiratory distress in neonates and infants. CLE is the most common cystic pulmonary malformation in our institution.

Cardiac rhabdomyoma is the most common cardiac tumour in childhood and is often associated to tuberous sclerosis (TS). However, a neonatal cardiac failure was uncommonly reported as the first manifestation of tuberous sclerosis.We report a case of a cardiac tumour revealed by a heart failure in a newborn who developed later clinical manifestations of TS.We report a case of a seven-day-old girl, admitted for cardiac failure. Echocardiography discovered a voluminous single mass in the right ventricle that affected partially heart output consistent with rhabdomyoma. Clinical course improved with symptomatic treatment. Seven months later, she developed generalized seizures associated to depigmental macules and facial neuro-fibroms. Cerebral magnetic resonance imaging showed cerebral hamartoms. Subsequent eight years follow-up revealed a spontaneous regression of cardiac rhabdomyoma and no further cardiac manifestations in contrast to a slight debility and a partial control of epilepsy.A cardiac rhabdomyoma discovered in neonates is a good indicator of TS suggesting careful followup and management

The aim of this report is to determine clinical characteristics and outcome of Cystic Fibrosis (CF).Cases of CF managed at Infantile Medicine A Department in Children's Hospital of Tunis during 13 years (1994-2006) were reviewed.16 children had CF. They were 8 males and 8 females. 13 patients were consanguineous and four had similar familial cases. The mean age at diagnosis was 19 months (10 days, 13 years). 3/4 of patients were symptomatic within the first trimester of life. Revealing symptoms were: obstructive bronchopathy associated to chronic diarrhea (n=6), edema-anemia-hypotrophy-hypoproteinemia syndrome (n=3), meconium ileus (n=4), bronchiectasis (n=2) and chronic diarrhea (n=1). The diagnosis was confirmed by sweat test and genotypic data. The F508 del was the most frequent mutation (54%). Clinical outcome was characterized by the occurrence of respiratory and nutritional complications: acute respiratory failure (n=6), chronic respiratory failure (n=3), chronic pseudomonas aeruginosa infection (n=6) at a medium age of 3.8 years, recurrent haemoptysis (n=2), pleural effusion (n=2), a malnutrition (n =10) and diabetes associated to puberty delay in one patient. Seven patients died at mean age of 4.4 years (6 months, 17.3 years). Among surviving patients, six had no compromised nutritional status or lung function. Prenatal diagnosis was performed in three families.CF is characterized by earliest onset and severity of symptoms. Therapeutic insufficiency is the main cause of precocious complications and poor prognosis in our series.

SummaryWe report a case of a 1-month-old boy who has developed respiratory distress. Chest X-ray and CT scan showed over distension of the left upper lobe and a mediastinal shift in favour of congenital lobar emphysema (CLE) of the left upper lobe. One month after uneventful lobectomy, he was readmitted at hospital for another episode of respiratory distress. Chest radiography revealed relapse of compressive emphysema in the remaining left lobe. Gastro oesophageal transit and MRI were performed, which have shown a mediastinal cystic mass. Accordingly, the patient underwent thoracotomy. Surgical examination found a subcarinal bronchogenic cyst which compressed the main left bronchus, causing the CLE of both upper and lower left lobes. Histological examination of removed cyst confirmed these data. Authors discuss causes of diagnostic delay.

Asthma in infants is characterized by recurrence of three episodes of dyspnea and wheezing within two first years of age. Asthma in infancy is a heterogeneous condition with different clinical phenotypes and outcome. So, the diagnostic and therapeutic approach are often difficult. THE AIM of this systematic review was to provide answers to the following questions in the management of recurrent wheeze in infants: is it asthma?, should we treat wheezy infants?, what are the modalities of prescriptions? what is the long term outcome of wheezy infants?Electronic literature search was performed in Medline. Key-words used for the final search were "infant", "wheezing", "atopy", "asthma", "inhaled corticosteroids". We considered for analysis meta analysis, randomized controlled trials, systematic reviews, cohort studies and consensus statement reports.The diagnosis of asthma in infants is more difficult than in older children or adults since many causes of eezing" may simulate an asthma associated to difficulties to evaluate bronchial hyper responsiveness in this age. There are three groups of wheezy infants: transient early wheezers, persistent non atopic wheezers and persistent atopic wheezers or asthmatic. Since recent data have proved early bronchial inflammation in wheezy infants, inhaled corticosteroids have become the main treatment. However, management of asthmatic infants is more difficult according to anatomic and functional respiratory peculiarities. There is no reliable clinical or biological indicators of future asthma. The evidence of atopy in infants with recurrent wheezing seems to be the main risk factor of the development of persistent asthman.

Summary Aim The aim of this report was to screen for celiac disease (CD) in patients with idiopathic pulmonary hemosiderosis (IPH). Patients and methods Patients with IPH treated at the Children's Hospital of Tunis between 1976 and 2006 were reviewed and investigated for CD, using serological and histological tests. Results A total of 10 children (two boys and eight girls) had IPH. The mean age at diagnosis was 3.1 years. Three had digestive symptoms and positive CD serology, which was confirmed by histological data. Clinical and radiological findings improved markedly in all CD patients with corticosteroid treatment combined with a gluten-free diet. Symptoms of IPH and CD both returned in one patient who stopped the gluten-free diet. Conclusion Three of our 10 patients with IPH also had CD. These data illustrate the close etiopathogenic link between IPH and CD, and strongly suggest that CD be looked for in IPH patients, especially in those with symptoms suggestive of CD.

International audience; BACKGROUND: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. OBJECTIVE: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. METHODS: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. RESULTS: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. CONCLUSION: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.

Summary Background The haematological abnormalities are common in patients with tuberculosis (TB). However, autoimmune bicytopenia is extremely rare in childhood TB. Case report A 11-year-old girl presented with 4-week history of fever and cough associated to weight loss. The diagnosis of active pulmonary TB was achieved based on radiological and microbiological findings. Simultaneously, laboratory investigations revealed autoimmune haemolytic anaemia associated to immune thrombocytopenia. These haematological disorders were successfully treated with anti-tubercular drugs only. Conclusion Tuberculosis should be included in the etiological investigation of autoimmune “cytopenias” in childhood, specially in endemic countries, since they may respond to anti-tubercular drugs.