Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT). PH1 is a clinically and genetically heterogeneous disorder. The aim of our study was to analyze and characterize the mutational spectrum of PH1 in Tunisian patients. MATERIALS AND METHODS: Molecular studies of 146 Tunisian patients suspected with PH were performed by PCR/Restriction fragment length polymorphism (RFLP) to detect seven mutations described as the most common. Direct sequencing for the 11 exons was performed in patients in whom any mutation was not identified. RESULTS: The genetic diagnosis of PH1 was confirmed in 62.3% of patients. The first molecular approach based on PCR/restriction enzyme test was positive in 37.6% of patients, whereas the second molecular approach based on whole gene sequencing was successful in 24% of cases. Twelve pathogenic mutations were detected in our cohort. Two mutations were novel, and five were detected for the first time in Tunisians. The three most frequent mutations were p.Ile244Thr, p.Gly190Arg, and c.33dupC, with a frequency of 43.4%, 21.4%, and 13.1%, respectively. CONCLUSION: The two novel mutations detected in our study extend the spectrum of known AGXT gene mutations. The screen for the mutations identified in this study can provide a useful, cost-effective, and first-line investigation in Tunisian PH1 patients.

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.

A Founder Effect of c.257 + 2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients.

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.

X-Linked Agammagobulinemia in a Large Series of North African Patients: Frequency, Clinical Features and Novel BTK Mutations.

PURPOSE: X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. METHODS: Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2% peripheral B cells were enrolled. The search for BTK gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing. RESULTS: We identified 33 different mutations in the BTK gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5% vs. 85%). No strong evidence for genotype-phenotype correlation was observed. CONCLUSIONS: This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.

Report of the Tunisian Registry of Primary Immunodeficiencies: 25-Years of Experience (1988-2012).

PURPOSE: Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to not only recurrent infections but also autoimmune diseases and malignancies. The aim of this study was to describe and analyze the distribution, clinical features and eventual outcome of PID among Tunisian patients. METHODS: We reviewed the record of 710 patients diagnosed with Primary Immunodeficiency Diseases (PIDs) from the registry of the Tunisian Referral Centre for PIDs over a 25-year period. RESULTS: The male-to-female ratio was 1.4. The median age at the onset of symptoms was 6 months and at the time of diagnosis 2 years. The estimated prevalence was 4.3 per 100,000 populations. The consanguinity rate was found in 58.2 % of families. According to the International Union of Immunological Societies classification, spectrums of PIDs were as follows: combined T-cell and B-cell immunodeficiency disorders account for the most common category (28.6 %), followed by congenital defects of phagocyte (25.4 %), other well-defined immunodeficiency syndromes (22.7 %), predominant antibody deficiency diseases (17.7 %), diseases of immune dysregulation (4.8 %), defect of innate immunity (0.4 %) and complement deficiencies (0.4 %). Recurrent infections, particularly lower airway infections (62.3 %), presented the most common manifestation of PID patients. The overall mortality rate was 34.5 %, mainly observed with combined immunodeficiencies. CONCLUSION: The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of Combined Immunodeficiencies and phagocyte defects in number and/or function. More is needed to improve PID diagnosis and treatment in our country.

A 1,100-year-old founder effect mutation in IL12B gene is responsible for Mendelian susceptibility to mycobacterial disease in Tunisian patients.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder predisposing apparently healthy individuals to infections caused by weakly virulent mycobacteria such as bacille Calmette-Guerin (BCG), environmental mycobacteria, and poorly virulent Salmonella strains. IL-12p40 deficiency is the first reported human disease due to a cytokine gene defect and is one of the deficiencies that cause MSMD. Nine mutant alleles only have been identified in the IL12B gene, and three of them are recurrent mutations due to a founder effect in specific populations. IL-12p40 deficiency has been identified especially in countries where consanguinity is high and where BCG vaccination at birth is universal. We investigated, in such settings, the clinical, cellular, and molecular features of six IL-12p40-deficient Tunisian patients having the same mutation in IL12B gene (c.298_305del). We found that this mutation is inherited as a common founder mutation arousing ~1,100 years ago. This finding facilitates the development of a preventive approach by genetic counseling and prenatal diagnosis especially in affected families.

Clinical, immunological and genetic findings of a large tunisian series of major histocompatibility complex class II deficiency patients.

INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Idiopathic pulmonary hemosiderosis and stroke secondary to protein C deficiency in a child with Down syndrome: a case report.

BACKGROUND: Patients with Down syndrome are at a higher risk of developing autoimmune disorders such as thyroiditis, diabetes, and celiac disease compared with the general population. Although some diseases are well known to be associated with Down syndrome, others such as idiopathic pulmonary hemosiderosis and ischemic stroke due to protein C deficiency remain rare. CASE PRESENTATION: We report a case of a 2.5-year-old Tunisian girl with Down syndrome and hypothyroiditis admitted with dyspnea, anemia, and hemiplegia. Chest X-ray showed diffuse alveolar infiltrates. Laboratory tests showed severe anemia with hemoglobin of 4.2 g/dl without hemolysis. A diagnosis of idiopathic pulmonary hemosiderosis was confirmed by bronchoalveolar lavage showing numerous hemosiderin-laden macrophages, with a Golde score of 285 confirming the diagnosis of pulmonary hemosiderosis. Concerning hemiplegia, computed tomography showed multiple cerebral hypodensities suggestive of cerebral stroke. The etiology of these lesions was related to protein C deficiency. CONCLUSION: Idiopathic pulmonary hemosiderosis remains a severe disease, which is rarely associated with Down syndrome. The management of this disease in Down syndrome patients is difficult, especially when associated with an ischemic stroke secondary to protein C deficiency.

Clinical and radiological findings of posterior reversible encephalopathy syndrome in children: About 16 children hospitalized in the pediatric department of a Tunisian tertiary care hospital.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity most frequently described in young- or middle-aged adults with a rare occurrence among children. AIM: To determine the clinical, radiological features and outcome of PRES in children admitted to a Tunisian tertiary care pediatric department. METHODS: we retrospectively reviewed records of all children under 18 years old diagnosed with PRES and admitted to the PICU of the Pediatric department of Sahloul University Hospital from January 2000 to August 2021. RESULTS: Sixteen patients were enrolled in this study. The mean age of the study population at PRES onset was 10 years (range: 4-14 years) and the male female ratio was 3. The most frequent neurological signs were seizures (n = 16 cases), headache (n = 8 cases), and impaired level of consciousness (7 cases). Visual disturbances were found in one patient. Arterial hypertension was the most underlying cause (16 cases). Brain MRI showed vasogenic edema, mostly localized in the parietal (13 cases) and occipital (11 cases) lobes. Moreover, cytotoxic edema (2 cases), pathologic contrast enhancement (1 case), and hemorrhage (3 cases) were isolated on MRI. The outcome after specific management was favorable after the first onset in 13 cases and death occurred in 3 patients. Relapses were observed in 4 patients. CONCLUSION: Clinical features presented by children with PRES are variable and non-specific. MRI typically shows reversible posterior cerebral edema. However, in some cases, atypical neuro-imaging findings, such as cytotoxic edema infarction, hemorrhage and contrast enhancement can be observed.

Epidemiological, Bacteriological, and Evolutive Features of Children Hospitalized for Infective Endocarditis in a Tertiary Tunisian Pediatric Department.

Background: Infective endocarditis is a rare condition in childhood, and there is limited data on this disease in Tunisia. Objective: This study aims to analyze the epidemiological profile, bacteriological data, and prognosis of infective endocarditis in children admitted to the pediatric department of a University Hospital in Tunisia. Methods: We conducted a comparative cross-sectional study in the pediatric department of Sahloul Teaching Hospital in Sousse, a tertiary referral hospital in Tunisia. The study included all children aged ≤ 18 years with infective endocarditis admitted to the tertiary referral center for pediatrics in Sahloul University Hospital from January 1994 to December 2022. The diagnosis of infective endocarditis was based on modified Duke's criteria. Results: Thirty-six patients met the diagnostic criteria for infective endocarditis, resulting in a proportion of 07 cases per 1000 hospital admissions. The mean age was 6 years (range: 40 days to 16 years). Congenital heart disease was identified as the underlying lesion in 23 cases (63.9 %). Blood cultures were positive in 20 patients (55.6 %), predominantly with Staphylococcus species (55 %). The most frequent complications involved the central nervous system (8 cases; 22.2 %). The mortality rate was 25 %, and factors predicting mortality included heart failure on admission or during the hospital stay, increased leukocyte count, and decreased prothrombin time. Conclusion: Our study reveals a shift in the prevalent underlying lesions, with rheumatic heart diseases no longer being the most common. Staphylococcus spp. emerged as the predominant organism in blood cultures. Notably, mortality predictors included heart failure, an elevated leukocyte count, and a decreased prothrombin time rate.

X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production.

Germline mutations in five autosomal genes involved in interleukin (IL)-12-dependent, interferon (IFN)-gamma-mediated immunity cause Mendelian susceptibility to mycobacterial diseases (MSMD). The molecular basis of X-linked recessive (XR)-MSMD remains unknown. We report here mutations in the leucine zipper (LZ) domain of the NF-kappaB essential modulator (NEMO) gene in three unrelated kindreds with XR-MSMD. The mutant proteins were produced in normal amounts in blood and fibroblastic cells. However, the patients' monocytes presented an intrinsic defect in T cell-dependent IL-12 production, resulting in defective IFN-gamma secretion by T cells. IL-12 production was also impaired as the result of a specific defect in NEMO- and NF-kappaB/c-Rel-mediated CD40 signaling after the stimulation of monocytes and dendritic cells by CD40L-expressing T cells and fibroblasts, respectively. However, the CD40-dependent up-regulation of costimulatory molecules of dendritic cells and the proliferation and immunoglobulin class switch of B cells were normal. Moreover, the patients' blood and fibroblastic cells responded to other NF-kappaB activators, such as tumor necrosis factor-alpha, IL-1beta, and lipopolysaccharide. These two mutations in the NEMO LZ domain provide the first genetic etiology of XR-MSMD. They also demonstrate the importance of the T cell- and CD40L-triggered, CD40-, and NEMO/NF-kappaB/c-Rel-mediated induction of IL-12 by monocyte-derived cells for protective immunity to mycobacteria in humans.

[Coronary artery aneurysm in Kawasaki disease and its risk factors : a retrospective study about 65 Tunisian children]. / Les complications coronaires de la maladie de Kawasaki et ses facteurs de risque : à propos de 65 cas d'enfants tunisien.

INTRODUCTION: Kawasaki syndrome (KS) is a systemic vasculitis of unknown etiology that affects medium and small blood vessels. The aim of our study is to analyze coronary artery lesions in children with KS and their risk factors. MATERIAL AND METHODS: All children under the age of 15 years-old presenting KS and admitted in the pediatric department of three university hospital (Sahloul hospital, and Farhat Hached hospital of Sousse, Ibn El Jazzar hospital of Kairoun) from January 2000 to December 2018 were included. RESULTS: Sixty-five patients were included in our study. The mean age at diagnosis was of 29.9 months [2-120 months] and the sex ratio was of 1.7. Echocardiography was performed in all patients. It showed coronary dilation in 37% of patients with coronary artery diameter of 4.2 mm on average [3.2-7mm]. The coronary aneurysm was small in 19 cases and medium in 5 cases. No giant aneurysm has been identified. In univariate analysis, the predictors of coronary artery lesions were male sex, atypical form, fever duration more than 10 days, hepatic cytolysis, thrombocytosis and anemia. In multivariate analysis, only the last four parameters were the predictive factors of the coronary artery involvement. CONCLUSION: Several risk factors can be used to determine which children are predisposed to develop coronary dilations. In case of patient with risk factors, intravenous immunoglobulins should be initiated early to avoid these serious complications.

Acute disseminated encephalomyelitis: A retrospective study of 20 children in a pediatrics department in Tunisia.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder of the central nervous system. Little information is available about the clinical and neuroradiological profile or the follow-up of this disease in Tunisian children. AIM: To determine the clinical, laboratory, and radiological features and the outcome of ADEM in children admitted to the pediatrics department of a university hospital in Tunisia. METHODS: All children ≤ 18 years old presenting with ADEM and admitted to the tertiary referral center for pediatrics at Sahloul University Hospital from January 2000 to December 2020 were included in the study. The diagnosis of ADEM was confirmed according to the international pediatric multiple sclerosis study group criteria. RESULTS: A total of 20 patients (13 girls and 7 boys) fulfilled the diagnostic criteria for ADEM. The mean age at diagnosis was 5.6 years. The clinical presentation included polyfocal neurological signs such as cranial hypertension (45%), seizures (35%), and motor weaknesses (55%). Pyramidal tract signs and cranial nerve palsies were noted in 55% of cases. Brain magnetic resonance imaging showed particular features, namely, a relapsing tumor-like form in one case, and optic neuritis and demyelinating lesions of the white matter in the brain and the spinal cord with gadolinium cerebral ring-like enhancement in another case. The treatment consisted of intravenous immunoglobulin in 16 cases (80%) and corticosteroid in 19 cases (95%). Plasmapheresis was used for one patient. Complete recovery was observed in 12 patients (60%); 19 patients (95%) had a monophasic course of the disease while only one patient developed multiphasic ADEM. CONCLUSIONS: ADEM remains a difficult diagnosis in children. Nevertheless, after prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with restitutio ad integrum.

[Phenotype and mutational spectrum in Tunisian pediatric gaucher disease]. / Phénotype clinique et spectre mutationnel de la maladie de Gaucher pédiatrique en Tunisie.

BACKGROUND: Gaucher disease (GD) is a sphingolipidosis with heterogeneous phenotypic expression. The vital and / or functional prognosis may be threatened by an early visceral severe involvement in type 1 or a neurological degeneration in the more rarest neuroneupathic forms. The phenotypic and genotypic data regarding Gaucher disease are poorly known in Maghrebian countries; they are even less for pediatric forms. THE AIM of the study is to highlight the specific phenotypic and genotypic changing among the widest Gaucher pediatric cohort in the Tunisian population. METHODS: a restrospective study of a sample oh children in voluved by gaucher disease. RESULTS: Twenty one cases of GD were identified, divided into 13 cases with type 1, 5 with type 3 and 3 children with acute neurological form. The first symptoms occurred before 1 year age in one third of patients with type IGD. The clinical phenotype was severe according to the high severity score index and proportion of growth retardation. Portal hypertension was found in 8 patients. Three type 3 GD patients died before occurrence of the neurological signs. The phenotype was intermediate between the classic type 2 GD and its perinatal lethal variant. Three patients were treated with enzyme replacement therapy and 4 others had allogenic bone marrow transplantation with a favorable outcome. Three mutations dominate the genotypic spectrum of GD in this cohort. Additionally to the N370 mutation, L444P and RecNciI mutations seem to occur more frequently compared to the GD forms presenting in adulthood. CONCLUSION: This data confirm the particular severity of Gaucher disease manifesting in childhood. This was enhanced through the high frequency of severe mutations. Further studies on largest cohort are needed to more clarify the phenotypic and genotypic features of Gaucher disease in Tunisia.

Incidence of mucopolysaccharidoses in Tunisia.

BACKGROUND: The mucopolysaccharidoses (MPS) are a devastating heterogenous group of lysosomal storage disorders. AIM: To evaluate the epidemiological profile of MPS in Tunisia. METHODS: we conducted a retrospective epidemiological survey covering the period 1970-2005. Multiple sources were used to identify affected patients. RESULTS: Ninety six confirmed MPS cases were collected from 132 suspected cases found in the surveyed data. Of the ninety six confirmed cases, 20% were from multiplex families. Consanguinity was found in 83% of the families. The crude rate for all types of mucopolysaccharidoses was 2.3 cases in 100,000 live births. The prevalence of MPS type I, III and IV, those most frequently occurring in the collected data, were estimated at 0.63, 0.7 and 0.45 per 100,000 live births, respectively. The cumulative incidence of MPS type VI (0.3 per 105 live births) was higher than reported in European countries; but, it is likely that... CONCLUSION: The reported frequency of all types of MPS in Tunisia is underestimated.

[Uremic and haemolytic syndrome in children: study of 17 cases]. / Syndrome hémolytique et urémique de l'enfant: Etude de 17 observations.

BACKGROUND: In spite of its rarity, the haemolytic and uremic syndrome (HUS) constitutes the first aetiology of acute renal insufficiency (ARI) in child. AIM: The aim of this work is to analyze clinical and evolutive aspects of the HUS in child. METHOD: We studied retrospectively 17 cases of HUS in child enrolled in the paediatrics' department of Sahloul Hospital during eight years period (1996 to 2003). RESULTS: It is about four boys and 13 girls (sex-ratio = 0.3) aged three months to nine years (mean age: 32 months). Typical HUS was observed in eight child and atypical HUS in the nine others which three presenting a familial form and one associated with steroid resistant nephrotic syndrome. Diagnosis of HUS was established on the classic triad of the disease (anaemia, thrombopenia and ARI) and/or by the histology. Extra-renal manifestations (neurological or digestive involvement) were observed in 11 patients. A blood transfusion was indicated in 13 patients presenting severe anaemia. Peritoneal dialysis was indicated for nine patients while three others required haemodialysis because renal insufficiency had evolved quickly to the end stage. Thirteen cases of HUS (eight typical and five atypical) have received plasma therapy during two to five days. The short-term evolution was favourable with recuperation of normal renal function in seven cases (five with typical SHU and two with atypical SHU). Three children developed terminal renal insufficiency and were currently in haemodialysis. Five patients (four cases of atypical HUS and one case of typical HUS) died of the continuations of the ARI and/or nosocomial infection. CONCLUSION: The HUS remains a serious illness because of the risk of complications that can occur to short and long-term. Currently, the specific treatment is only recommended in patients presenting an atypical form of HUS.

[Pediatric celiac disease in the region of Sousse: epidemiological and evolutive study of 80 cases]. / Maladie coeliaque de l'enfant dans la région de Sousse: étude épidémiologique et évolutive de 80 cas.

AIM: Analyze epidemiological and evolutive profile of paediatric celiac disease in the region of Sousse. METHODS: We studied retrospectively 80 cases enrolled in the paediatrics' department of Sousse between 1993 and 2003. RESULTS: There were 44 girls and 36 boys (sex-ratio=0.81). The middle age of gluten introduction was 9 months, with extremes going from 1 to 24 months. Free interval between the introduction of gluten and the beginning of the symptoms was meaningfully more elevated in patients who received gluten after the age of 6 months (p=0.036). At the time of the diagnosis, the middle age of our patients was six years with extremes going from nine months to 17 years. The classic form of celiac disease with chronic diarrhoea has been observed in 85% of the cases. The morbid associations with celiac disease were dominated by the diabetes type 1 noted in 5% of the cases. Antigliadin antibodies, practiced in first intension, were positive in 98.6%. At histology, villous atrophy was sub-total to total in 96.25% of the cases and partial in 3.75% of the cases. Follow-up was on average at 18 months. Adhesion to the gluten-free diet (GFD) was judged satisfactory in 81.45% of the cases on average. Catch up growth, although remarkable, was not very satisfactory. Indeed, several patients adhering little or not to the GFD kept, at one year of evolution, a ponderal and stature delay superior to 2SD.

[Complete primary distal renal tubular acidosis in children: 11 cases]. / L'acidose tubulaire distale complete et primitive de l'enfant à propos de 11 observations.

AIM: Analyze the clinical and evolutive particularities of complete primary distal renal tubular acidosis in children, METHODS: We studied retrospectively 11 cases enrolled in the pediatrics department of Sousse during 10 years period (1993-2002). RESULTS: It is about 9 boys and 2 girls (sex-ratio = 45) aged 3 month to 5 years (mean age: 18 months). Diagnosis was suspected on clinical and biological data of presumption and confirmed by acidification test. Radiological investigation objectified a nephrocalcinosis in eight patients and urinary lithiasis in two other cases. Auditive exploration showed sensorineural deafness in three patients. The illness appears sporadic in two cases and autosomal recessive in nine other cases. After alkali treatment (sodium bicarbonate), evolution was globally favorable.

[Graves's disease in children and adolescent: study of seven cases]. / La maladie de Basedow chez l'enfant et l'adolescent: etude de sept cas.

BACKGROUND: In spite of its rarity in the paediatric age, Graves' disease constitutes the principal aetiology of hyperthyroidism in child. AIM: Our goal is to analyze the clinical and evolutive particularities of Graves's disease in children. METHODS: We studied retrospectively seven cases of Graves' disease in children enrolled in the pediatrics department of Sousse during ten years period (1993-2002). RESULTS: There were six girls and one boy (sex - ratio = 0.16) aged 4.5 to 16 years (mean age: nine years and one month). The diagnosis has been established clinically on the presence of classic symptoms of the illness associated to the biological and radiological findings. As part of research of possible associations with this illness, we observed solely in a case, in addition of Graves's disease, the coexistence of Down syndrome and coeliac disease, rarely described. Among the HLA antigens predisposing the Graves's disease, we only found HLA B8 antigen in a patient. The evolution under antithyroid drug treatment (ATD) has been marked by fast disappearance of functional signs in all patients. However, biological and clinical euthyroidism was more difficult to achieve. The treatment has been stopped in only one patient after 40 months period. CONCLUSION: Graves' disease is usually easy to recognize but difficult to treat. Radical treatments (thyroidectomy or radioactive iodine therapy) are indicated in second intention after having tempted ATD beforehand.

Rhombencephalosynapsis diagnosed in childhood: clinical and MRI findings.

Rhombencephalosynapsis (RES) is a rare cerebellar malformation of unknown etiology characterized by vermal agenesis or hypogenesis, fusion of hemispheres and the dentate nuclei. Clinical presentation and prognosis are extremely variable and generally depends one the associated supratentorial anomalies. We report the first Tunisian case of RES diagnosed by magnetic resonance imaging (MRI) in a 3.5-year-old boy born to consanguineous parents. The child had spastic diplegia, facial dysmorphia, skeletal anomalies and normal intellectual development. Additional supratentorial anomalies were agenesis of septum pellucidum, moderate hydrocephalus and hypogenesis of corpus callosum. In this paper, the clinical and MRI findings and possible pathogenesis of this disorder are discussed.