S. Abroug

Centre Hospitalier Universitaire de Sahloul, Justiniapolis, Sūsah, Tunisia

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Publications (57)55.72 Total impact

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    ABSTRACT: The β hemoglobinopathies [β-thalassemia (β-thal) and structural hemoglobin (Hb) variants such as Hb S (HBB: c.20A > T) and Hb E (HBB: c.79G > A)] are among the most common inherited diseases worldwide. In Tunisia, due to the high prevalence of consanguineous marriages, the recurrent risk of this disease is high. The average prevalence of hemoglobinopathies is 4.48%, reaching 12.50% in some focus regions. The molecular investigations on thalassemia contributed to establishing the spectrum of mutations in the Tunisian population. The total number of HBB gene mutations identified was 24. The two most frequent mutations, codon 39 (C > T) (HBB: c.118C > T) and IVS-I-110 (G > A) (HBB: c.93–21G > A) accounted for 70.0% of the total encountered β-thal cases. These two mutations together with IVS-I-2 (T > G) (HBB: c.92 + 2T > G) and the Hb S variant account for more than 90.0% of all HBB genetic variants in Tunisia. Thus, developing rapid, inexpensive and reliable mutation-specific molecular diagnostic assays targeting our Tunisian populations is our aim to facilitate routine detection of hemoglobinopathies. In this report, we describe the successful application of the multiplex minisequencing assay as an alternative strategy for genetic diagnosis of HBB gene disorders in Tunisia.
    No preview · Article · May 2015 · Hemoglobin
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    ABSTRACT: 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.
    Full-text · Article · Oct 2014 · Genetic Testing and Molecular Biomarkers
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    ABSTRACT: Introduction Central diabetes insipidus (CDI) or neurohypophyseal diabetes insipidus is a rare disorder in children caused by an inadequate release of the antidiuretic hormone, arginine vasopressin (AVP). CDI is clinically caracterised by polyuria and polydipsia. Methods and materials Clinical, auxological, biological and neuroradiological characteristics of 10 children with central diabetes insipidus (CDI) were retrospectively analysed during a period of 18 years. Results Five girls and five boys with permanent diabetes insipidus were enrolled in the study. The mean age at diagnosis was 6 years five months (range: 4 months -14 years). The major cumulative and often subtle presenting manifestations were: polyuria (n = 10), polydipsia (n = 10), fatigue (n = 2), growth retardation (n = 4), headache (n = 1). All patients had low urine osmolality and elevated plasma osmolality on diagnosis. The aetiology of central DI was organic in 8 patients, craniopharyngioma in 3 patients, Langerhans cell histiocytosis in 2 patients, neurosarcoidosis in one case, Pituitary stalk interruption in one patient and wolfram syndrome in one patient. Three patients had anterior pituitary hormone deficiency and growth hormone deficiency. Polyuria and polydipsia have regressed in all patients put under desmopressin. Patients with craniopharyngioma were operated with a tumour recurrence in one case. Conclusion DIC is a rare disease in Paediatrics. The circumstances of discovery and positive diagnosis are often easy. The underlying aetiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Recurrent bacterial meningitis is an uncommon disease of childhood. It occurs most often in children who have an underlying predisposing disorder that can result from anatomic fistula or immunodeficiency. Cochleovestibular dysplasia is a rare malformation of the inner ear that is often associated with translabyrinthine cerebrospinal fistula and then can cause recurrent bacterial meningitis. We report an unusual case of recurrent meningitis revealing cochleovestibular dysplasia in a 9-year-old child. The malformation was confirmed by imaging and the child had surgery. The outcome was favourable with no recurrence of meningitis during the 3 years after the operation.
    Full-text · Article · Oct 2014 · Archives de Pédiatrie
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    ABSTRACT: Introduction Tuberculosis (TBC) continues to cause an unacceptably high toll of disease and death among children worldwide, particularly in the developing countries. Objective Study the epidemiological and clinical aspects of TBC in Tunisian children and clarify its treatment. Population and methods A descriptive study was carried out, included all cases of TBC diagnosed in Sahloul paediatric unit hospital between 2004 and 2013. Epidemiological, clinical and microbiological data were recorded. Therapeutic and evolutionary aspects were clarified. Results We reviewed 32 cases (16 boys and 16 girls), aged from 6 months to 15 years. All patients were vaccinated against tuberculosis. No case of malnutrition none immune deficiency had been recorded until the first hospitalisation. The diagnosis of TBC was based on clinical features, tuberculin skin test, chest radiography and the histological examination of lymph node, peritoneal and pleural biopsy. Diagnoses were identified: Lymph node tuberculosis (11 cases), pulmonary tuberculosis (4 cases), peritoneal tuberculosis (4 cases), bone tuberculosis (4 cases), tuberculous meningitis (2 cases), cutaneous tuberculosis (1 case), renal tuberculosis (1 case), tuberculosis in hematopoietic stem cell (1 case), pleuro-pericarditis tuberculosis (1 case), and the disease has affected several organs (disseminated) in 3 cases. Two cases of congenital immunodeficiency syndrome were identified. All our patients were treated with an association of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol for 2 months, and then they received Isoniazid and Rifampicin for a period ranging from 2 to 16 months. 27 children were cured (24 without sequelae and 3 with sequelae). Two children died. Conclusion Tuberculosis in children presents particularly difficult challenges, but advances in paediatric tuberculosis research could provide wider insights and opportunities for tuberculosis control especially in developing countries.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Background Patients with congenital hypopituitarism might have the classic triad of pituitary stalk interruption syndrome (PSIS), which consists of: an interrupted or thin pituitarys talk, an absent or ectopic posterior pituitary (EPP), and anterior pituitary hypoplasia or aplasia. The most remarkable clinical manifestations of patients with PSIS was growth retardation. Objective To analyse the clinical, auxological and radiologic characteristics of the patients with PSIS to achieve better comprehension of this pathology. Methods Data of patients with PSIS were retrospectively analysed for the clinical, laboratory and imaging features. Results Five patients were included (4 girls and 1 boy). They are aged at the first clinical manifestation from 1 month to 3 years. The symptoms that led to the diagnosis were failure to thrive in four cases and polyuria-polydipsia syndrome in one case. A complete growth hormone deficiency was confirmed in four cases, one was complicated with central hypothyroidism and one was accompanied by central adrenocortical hypofunction. The last patient present only central diabetes insipidus. Hypothalamo-pituitary MRI was performed in all of the patients showed one or more elements of the classic triad. A causative mutation was studied in two patients. None HESX1 or LHX4 mutations was found. Conclusion The PSIS is relatively frequent. The outcome is progressive evolution towards panhypopituitarism. The treatment consists in hormone replacement therapy.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Introduction Langerhans cell histiocytosis (LCH) is characterised by a reactive clonal proliferation and accumulation of dendritic cells with a wide range of clinical presentations. Survival rate depend on single or multisystem disease. Objectives The aim of the study was to analyse the clinical, radiologic features and responses to treatment. Materials and methods We retrospectively reviewed the clinical data, histopathological, radiologic features, treatment modalities, and outcome of patients presenting with LCH. Results 9 patients were included with two brothers. There were 5 girls and 5 boys. Mean Age at diagnosis was 39 months. The main clinical feature was prolonged ferver (5 cases), and impaired general condition (3 cases). Skin involvement was present in 5 patients, otitis in 3 patients and 3 cases of lung injury with Spontaneous pneumothorax in one case. 3 different Tumour syndromes were observed at diagnosis. The most of patients present a multi-system disease. Radiologic finding showed 2 cases of bone involvement. The bone marrow involvement was present in 2 patients. Six patients received corticosteroid and vinblastine combination with the use of cyclosporine in 3 cases. One patient developed insipidus diabetes. Two patients dead. Conclusion Childhood Langherhans cell histiocytosis is a rare and poorly understood multi-system disease. Treatment decisions are difficult given the unpredictable course of the disease sometimes spontaneous, mainly for unifocal forms remissions. Patients with localised disease generally have a good prognosis and require minimal treatment. However, patients with lesions in ‘risk’ organs (liver, spleen, lung, bone marrow) have a worse overall prognosis regarding mortality and morbidity.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Background The term of precocious puberty signifies the onset of secondary sexual characters before the age of 9 years in the boys and 8 years in the girls. The first step in the clinical reflection is to decide whether the child has central or peripheral form of precocious puberty. Objective Identify some causes of precocious puberty, expose difficulty of management. Methods A retrospective study of medical records of children hospitalised in the Paediatric unit at Sahloul hospital in Tunisia. Results Within a period of 6 years, eight patients were diagnosed with precocious puberty (4 boys and 4 girls). The mean age was 4 years and 3 months. The precocious puberty was isosexual in all cases with accelerated growth velocity. The PP was identify as central in four cases, the investigations showed: hypothalamic hamartoma (2 cases), pituitary adenoma (1 case) and arachnoid cyst (1 case). Peripheral precocious puberty included: congenital adrenal hyperplasia (3 cases) and adrenocortical carcinoma (1 case). The children with central precocious puberty were treated with gonadotrophin releasing hormone agonists, those with congenital adrenal hyperplasia received steroids replacement therapy and surgery was performed for the boy with adrenocortical carcinoma. The clinical and biological evolution of our patients was favourable with a regression of signs of puberty and normal hormone levels after a mean of 5 years. Conclusion Precocious puberty needs a systematic approach with detailed history and clinical examination. Early treatment contributes to optimise adult height potential. There are still unresolved questions that future studies will need to address. Finally, the behavioural and psychological outcomes of precocious puberty were still poorly evaluated.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Introduction and Aims: According to classical nephrology practice, pure microscopic hematuria [MH] in early life is not considered a serious problem and up to date diagnostic studies are not always carried out. Family urine studies to confirm or rule out a familial disease should always be carried out early and if positive, molecular genetics should be used to study the whole family and establish the underlying genetic defect. Methods: During the last 30 years we have searched systematically in a homogeneous population of 650,000 people for familial MH and some 120 such families are under study so far. Molecular genetic studies during the last 10 years have led to the correct genetic diagnosis in 57 such families with a) 28 heterozygous COL4A3/A4 mutations and TBMN, b) 23 CFHR5 and C3 nephritis and c) 6 families with Alport syndrome. Results: Our most striking finding refers to the COL4A3/A4 heterozygous mutations that turn out to be the commonest cause of familial MH and have been identified in 249 carriers in 30 families. Some of these families are very big indeed and two of these mutations, COL4A3-G1334E and COL4A3-G871C, are particularly common. Mutation COL4A3-G1334E was found in 15 families and it accounts for 174 patients. C3 nephritis with the CFHR5 Cypriot mutation appears to be the 2nd commonest cause of familial MH with 150 carriers in 23 families. Classical XLAS, COL4A5 Alport was identified in 3 families with 9 affected males and 8 female carriers, while ARAS was also present in 3 additional families affecting 8 patients. Of the 249 patients with COL4A3/A4 heterozygous mutations 33 have reached ESKD and of the 150 CFHR5 patients 21 have reached ESKD. Conclusions: Our results strengthen the great significance of the heterozygous COL4A3/A4 mutations, not really well understood until after 1996, less than 20 years ago. These mutations are common, lead to TBMN and are the commonest cause of familial MH. More importantly however, these mutations lead much later in life to proteinuria, hypertension, CRF and ESKD and long term care is mandatory with prompt attention to the addition of proteinuria that requires urgent treatment. Heterozygous mutations COL4A3/A4 cause twice more patients to reach ESKD compared to classical XLAS and ARAS but fortunately at a much older age. Molecular genetics should be used more widely for an early diagnosis of this entity and more renal attention should be given to these patients to preserve kidney function and avoid ESKD.
    Full-text · Article · May 2014 · Nephrology Dialysis Transplantation

  • No preview · Article · Mar 2014 · Journal of Neuroradiology
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    ABSTRACT: Background Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the central nervous system, characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord. We aimed to assess the clinical presentations, neuroimaging, treatment, and outcome of eight children with ADEM. Methods An 11-years retrospective chart review of children with the diagnosis of ADEM was conducted during the period between 2000 and 2011. The diagnosis of ADEM was carried in front of clinical and radiological signs. Results Eight cases of ADEM, aged between 9 months and 14 years, were identified. The clinical picture is characterized by multiple symptoms. Prominent findings are seizures in three cases, altered level of consciousness in seven cases and motor system dysfunction in five cases. Brain magnetic resonance imaging evaluations had done in all patients and revealed demyelinated lesions in the cerebral cortex, subcortical white matter, in periventricular white matter, in deep gray matter and in brainstem in all patients. Spinal cord MRI was performed in one case and showed demyelinated lesions in cervical and dorsal etage. All patients were treated with high-dose intravenous methylprednisolone pulse therapy during six days, related by oral corticotherapy. Five of them received also intravenous immunoglobulins. The evolution was favorable in all patients, only one had mild long-term optic neuritis sequelae. Conclusion Clinical features of ADEM are similar to those of infectious encephalitis. The neuroimaging test of choice to establish the diagnosis is MRI. In most patients, the prognosis is good after treatment.
    Full-text · Article · Oct 2012 · Archives of Disease in Childhood
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    Preview · Article · Jan 2012 · Archives of Cardiovascular Diseases Supplements
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    Preview · Article · Jan 2012 · Archives of Cardiovascular Diseases Supplements
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    ABSTRACT: Primary hyperoxaluria type I (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. Four mutations (G170R, 33_34insC, I244T and F152I) account for more than 50% of PH1 alleles and form the basis for diagnostic genetic screening for PH1. We aimed to analyze the prevalence of these specific mutations causing PH1, and to provide an accurate tool for diagnosis of presymptomatic patients as well as for prenatal diagnosis in the affected families. Polymerase chain reaction/Restriction Fragment Length Polymorphism, were used to detect the four mutations in the AGXT gene in DNA samples from 57 patients belonging to 40 families. Two mutations causing PH1 were detected in 24 patients (42.1%), with a predominance of the I244T mutation (68% of patients) and 33_34insC (in the remaining 32%). In 92% of cases, mutated alleles were in homozygous state. The presented clinical features were similar for the two mutations. The age of onset was heterogeneous with a higher frequency of the pediatric age. In 58.3% of cases, the presentation corresponded to advanced renal disease which occurred early (< 5 years) in the two mutations. In adolescents, only the I244T mutation was detected (41.1%). I244T and 33_34insC mutations were observed in adult patients, with 17.6% and 12.5% respectively. Limited mutation analysis can provide a useful first line investigation for PH1. I244T and 33_34insC presented 28.2% of identified mutations causing disease in our cohort. This identification could provide an accurate tool for prenatal diagnosis in the affected families, for genetic counselling and for detection of presymptomatic individuals.
    Full-text · Article · May 2011 · BMC Nephrology
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    ABSTRACT: Steroid-resistant nephrotic syndrome (NS) remains one of the most intractable causes of end-stage renal disease in the first two decades of life. Several genes have been involved including NPHS1, NPHS2, WT1, PLCE1, and LAMB2. Our aim was to identify causative mutations in these genes, in 24 children belonging to 13 families with NS manifesting with various ages of onset. We performed haplotype analysis and direct exon sequencing of NPHS1, NPHS2, PLCE1, LAMB2, and the relevant exons 8 and 9 of WT1. Ten different pathogenic mutations were detected in seven families concerning four genes (NPHS1 (3/7), LAMB2 (2/7), NPHS2 (1/7), and WT1 (1/7)). Five of the detected mutations were novel; IVS9+2 T>C and p.D616G in NPHS1; p.E371fsX16 in NPHS2, and p.E705X and p.D1151fsX23 in LAMB2. Nine of 24 patients failed to be categorized by mutational analysis. Our study extends the spectrum of abnormalities underlying NS, by reporting novel mutations in the NPHS1 and NPHS2 genes and the first cases of LAMB2 mutations in Tunisia. Congenital and infantile NS can be explained by mutations in NPHS1, NPHS2, WT1, or LAMB2 genes. The identification of additional genes mutated in NS can be anticipated.
    No preview · Article · Feb 2011 · Pediatric Nephrology
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    ABSTRACT: B-type natriuretic peptide (BNP) is a biomarker of cardiovascular disease that is common in adults with chronic kidney disease (CKD). However, in children with CKD, the range and predictive power of BNP concentrations are not known. We aimed to determine the effect of HD on BNP, as well as the prognostic impact of BNP, in end-stage renal disease (ESRD) children undergoing hemodialysis (HD). Thirty-five children with chronic renal failure (16 boys age 12.1 ± 3.7 years) on maintenance HD were included. BNP level was measured, and Doppler echocardiography was performed 30 min before (pre-HD BNP) and 30 min after (post-HD BNP) HD in each patient. An adverse event was defined as all-cause death and heart failure hospitalization. The median pre-HD BNP, the post-HD BNP, and the change in BNP were, respectively, 240 pg/ml (72 to 3346), 318 pg/ml (79 to 3788), and 9 pg/ml (-442 to 1889). Pre-HD BNP concentration was negatively correlated with left ventricular (LV) ejection fraction (r = -0.41, P = 0.018). During a mean follow-up of 39 ± 14 months, 6 patients died, and 3 were hospitalized for heart failure. Using univariate analysis, BNP before and after HD as well as Doppler tissue imaging velocities had a strong graded relationship with adverse events. Cox proportional hazards model demonstrated that pre-HD body weight (P = 0.008), pre-HD BNP (P = 0.011), and post-HD BNP (P = 0.038) remained independent predictors of adverse outcome. Even in case of ESRD, BNP still strongly correlated with LV systolic and diastolic dysfunction and was associated with mortality in HD children.
    No preview · Article · Feb 2011 · Pediatric Cardiology

  • No preview · Article · Dec 2010 · Médecine et Maladies Infectieuses
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    ABSTRACT: Des données contradictoires existent concernant les changements induits par l’hémodialyse sur la fonction systolique et diastolique chez l’adulte. Peu de données concernant ce sujet chez l’enfant en insuffisance rénale terminale sont rapportées. Le but de ce travail est d’évaluer l’effet immédiat d’une séance d’hémodialyse sur la fonction systolique et diastolique ventriculaire gauche (VG) chez l’enfant en insuffisance rénale en utilisant l’échocardiographie Doppler conventionnelle et l’imagerie par Doppler tissulaire.
    No preview · Article · Feb 2010 · Annales de Cardiologie et d Angéiologie
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    ABSTRACT: We report 3 cases of primary oxalosis with nephrocalcinosis and severe renal failure. Extrarenal involvement was noted in bones in 3 cases, the heart in 2 cases, the central nervous system in 2 cases, the skin in 1 case and the eye in 1 case. The 3 patients presented with acute digestive disorders. Ultrasonography and CT scans showed digestive wall calcifications in addition to the classic appearance of primary oxalosis such as nephrocalcinosis or bone involvement. Primary hyperoxaluria is characterized by a calcium deposit in different tissues, mainly in kidneys. Digestive wall involvement has never been reported in the literature. Primary oxaluria should be considered in the presence of such a deposit in the gut wall.
    No preview · Article · Nov 2009 · Archives de Pédiatrie
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    ABSTRACT: Contrasting data exist about the hemodialysis induced changes of ventricular diastolic and systolic functions in adults. Few data in children with end-stage renal disease (ESRD) are reported. The aim of the present study was to evaluate the effect of a single hemodialysis (HD) session on left ventricular (LV) systolic and diastolic function using conventional pulsed-Doppler echocardiography and pulsed tissue Doppler imaging (TDI) in hemodialysis children. Thirty-five children with chronic renal failure (15 males, aged 12.8+/-3.8 years) on maintenance hemodialysis underwent conventional 2D and Doppler Echo together with measurement of longitudinal mitral annular motion velocities. Echocardiographic parameters were obtained 30 minutes before and 30 minutes after HD. Paired data were compared. Hemodialysis led to reduction in LV end-diastolic volume (p=0.001), end-systolic volume (p=0.05), left atrium area (p<0.0001), peak early (E wave) transmitral flow velocity (p=0.005), peak S velocity of pulmonary vein flow (p=0.002), aortic time velocity integral (p<0.0001) and aortic ejection time (p<0.0001). No significant change in Tei Index was observed after HD. Regarding TDI measures, velocities were not affected by preload reduction. Only the early diastolic velocities on the septal side of the mitral annulus decreased significantly (p=0.001) and the systolic velocities on the lateral side of the mitral annulus increased significantly (p=0.042) after hemodialysis. Most of Doppler-derived indices of diastolic function are preload-dependent. TDI velocities and Tei Index were not or minimally affected by preload reduction in hemodialysis children.
    No preview · Article · Oct 2009 · Annales de cardiologie et d'angeiologie