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.

Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III.

Glycogen storage disease type III (GSD III) is an autosomal recessive inborn error of metabolism caused by mutations in the glycogen debranching enzyme amylo-1,6-glucosidase gene, which is located on chromosome 1p21.2. GSD III is characterized by the storage of structurally abnormal glycogen, termed limit dextrin, in both skeletal and cardiac muscle and/or liver, with great variability in resultant organ dysfunction. The spectrum of AGL gene mutations in GSD III patients depends on ethnic group. The most prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe Islands. Here, we present the molecular and biochemical analyses of 22 Tunisian GSD III patients. Molecular analysis revealed three novel mutations: nonsense (Tyr1148X) and two deletions (3033_3036del AATT and 3216_3217del GA) and five known mutations: three nonsense (R864X, W1327X and W255X), a missense (R524H) and an acceptor splice-site mutation (IVS32-12A>G). Each mutation is associated to a specific haplotype. This is the first report of screening for mutations of AGL gene in the Tunisian population.

Thyroid-related autoantibodies in Tunisian patients with type 1 diabetes.

AIM: To evaluate, retrospectively, the frequency of antithyroid antibodies (ATA) in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: Antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (TG-Ab), and antithyroid-stimulating hormone receptor antibodies (TSHR-Ab) were determined by enzyme-linked immunosorbent assay. Sera of 312 patients (166 children and 146 adults) with T1D were analyzed. Sera of 276 healthy subjects (87 children and 189 blood donors) served as controls. RESULTS: Out of 312 patients with T1D, 44 (14%) had ATA (TPO-Ab or TG-Ab or TSHR-Ab). The frequency of ATA in patients with T1D was significantly higher than in the control group (14% vs. 2.8%; p<10(-5)). ATA were significantly more frequent in adult patients with T1D than in the blood donor group (20% vs. 1.6%; p<10(-8)). The frequency of ATA in adult patients was significantly higher than in pediatric patients (20% vs. 9%; p=0.006). The frequency of TPO-Ab and TG-Ab was significantly higher in patients with T1D than in the control group (13.5% vs. 2%; p<10(-8) and 7% vs. 2.2%, p=0.008), respectively. Out of 312 patients with T1D, only one had TSHR-Ab. The simultaneous presence of three autoantibodies was found in one patient with T1D. CONCLUSION: ATA were frequent in patients with T1D. Serological screening of autoimmune thyroid disease is suggested in patients with T1D.

[Idiopathic steroid-resistant nephrotic syndrome in child : study of 20 cases]. / Syndrome néphrotique idiopathique corticorésistant de l'enfant : Etude de 20 cas.

BACKGROUND: Idiopathic steroid-resistant nephrotic syndrome (ISRNS) is rare and represents a significant therapeutic dilemma for paediatricians and paediatric nephrologists. AIM: To analyze characteristics of the ISRNS in the child. METHODS: Retrospective study of 20 cases of ISRNS enrolled in paediatric department of nephrology in Sahloul hospital (Tunisia) between June 1993 and December 2007 (14 years period). RESULTS: There were eight girls and 12 boys (mean age: 5.8± 3.7 years) originating from the center or the south of Tunisia. Eight of them had a minimal-change disease (MCD), 11 a focal and segmental glomerulosclerosis (FSGS) and one a mesangioproliferative glomerulonephritis (MePGN). In this group, no family form could be identified. All patients were treated by cyclosporine associated with low dose of steroid. We noted a complete remission (CR) in nine cases, partial remission (PR) in three cases and no response to cyclosporine in eight cases. Among patients with CR, six presented MCD and three a FSGS. In this group, we observed relapse of nephrotic syndrome in six cases. End stage renal disease (ESRD) was noted in 10 patients of which five not responded to cyclosporine, two initially having presented a RC and three having since the beginning a PR. Among them, two only could be grafted; one relapses on transplant was observed with a single patient initially presenting a secondarily transformed MePGN in FSGS. CONCLUSION: Our study confirms the clinical, histological and evolutive heterogeneity of idiopathic steroid-resistant nephrotic syndrome. Although there is any therapeutic consensus in this domain, cyclosporine remains indicated in first intention in sporadic forms of ISRNS. On the other hand, renal transplantation constitutes the only therapeutic alternate in genetic forms that constantly evolve at ESRD.

Selected AGXT gene mutations analysis provides a genetic diagnosis in 28% of Tunisian patients with primary hyperoxaluria.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Novel mutations in steroid-resistant nephrotic syndrome diagnosed in Tunisian children.

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.

Contribution of laparoscopy in the abdominal tuberculosis diagnosis: retrospective study of about 11 cases.

OBJECTIVE: Abdominal tuberculosis is one of the most frequent extra-pulmonary localizations. Its diagnosis is difficult and may lead to a delayed prescription of specific treatment. This study is aimed at stressing the role of laparoscopy associated with a biopsy in the diagnostic confirmation of abdominal tuberculosis particularly in doubtful cases. METHODS: The diagnostic features of 11 cases hospitalized for abdominal tuberculosis in the Paediatric Surgery Department of Fattouma Bourguiba Hospital in Monastir for a 6-year period (2001-2006), were evaluated retrospectively. The diagnosis of abdominal tuberculosis was substantiated histopathologically by laparoscopy in all cases. The epidemiological and clinical characteristics along with the laboratory, radiological and histological data were studied. RESULTS: Eleven cases of abdominal tuberculosis with a mean age of 5.6 years were diagnosed. It was peritoneal tuberculosis in all cases and associated with intestinal localization in one case. A conversion to laparotomy was practiced in three patients: appendicular plastron in one case, pseudo-tumor aspect of an intestinal loop in another case and because of their pathological aspect appendicectomy and caecum biopsy in the third. The diagnosis was confirmed histologically by biopsies in nine cases and on excision pieces in the other two cases. All patients had an uneventful course with an antituberculosis treatment. CONCLUSION: Abdominal tuberculosis is still frequent in Tunisia. Because of its non-specific clinical presentation and the limited means of investigation, a laparoscopy with biopsy should be practiced as first line diagnostic tool in case of doubtful abdominal tuberculosis. The earlier the diagnosis is established and an adapted antituberculosis treatment is started, the better the prognosis is.

[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.

[Primary hyperoxaluria in children in central Tunisia]. / Hyperoxalurie primitive chez l'enfant au centre Tunisien.

AIM: The goal of this work is to analyze clinical and therapeutics particularities of primary hyperoxaluria in children in Tunisian centre. METHODS: We studied retrospectively 15 cases of primary hyperoxaluria enrolled during 9 years period (1994-2002). RESULTS: It is about 2 boys and 13 girls (sex - ratio = 4.5) aged 2 month to 13 years (mean age: 4 years). Six patients presented the infantile form and nine the juvenile form of HP. At the moment of diagnosis, renal function was normal in one patient, moderately altered in another and severely altered in the other patients. All patients had nephrocalcinosis and 6 among them radio-opaque renal calculi associated. Diagnosis of HP was established in 11 cases by hyperoxaluria and/or important hyperoxalemia or on the data of the renal biopsy and biochemical analysis of renal calculi in 4 cases. The so-called "maghrebin" mutation (Ile244Thr) sought-after in 9 children, has cannot be identified that in 2 among them. Eight patients died of the continuations of their illness. The seven other patients again in life present a terminal renal insufficiency treated by haemodialysis. No patient could benefit from organ transplantation. CONCLUSION: Primary hyperoxaluria is a very heterogeneous disease on the plan clinic that genetic. In Tunisia where it constitutes a frequent cause of end stage renal failure, prenatal diagnosis of this disease is of a big interest.

Screening by anti-endomysium antibodies for celiac disease in Tunisian children with type 1 diabetes mellitus.

AIM: Celiac disease (CD) and type 1 diabetes mellitus (DM1) can frequently coexist, presumably due to a common genetic predisposition. The present study was designed to evaluate the frequency of CD among Tunisian children with DM1. PATIENTS AND METHODS: A total of 205 diabetic children (92 girls, 113 boys, age range 6 months-15 years, median 11 years) were screened for CD by determination of IgA anti-endomysium antibodies (EMA). RESULTS: EMA were positive in 17 out of 205 (8.3%) children with DM1. The median age of DM1 at onset was significantly lower in patients with EMA than those without EMA (P<10(-7)). In 13 of 17 EMA-positive patients, duodenal biopsy could be performed and a destructive type of CD was confirmed in 11 of them: 8 patients showed total villous atrophy, 3 patients showed a partial villous atrophy. The other two patients showed a normal histological picture with normal number of intraepithelial lymphocytes. Parents of the remaining EMA-positive children refused endoscopy. Thus the prevalence of biopsy-proven CD was 5.3% (11/205). It was 7.6% (7/92) in girls and 3.5% (4/113) in boys but the difference was not statistically significant. Seventy three percent of patients with CD were asymptomatic. CONCLUSIONS: The prevalence of clinically unrecognized CD, found by EMA screening, is high in Tunisian children with DM1. We suggest that children with diabetes should be screened for CD.

[Henoch Schonlein purpura in children: clinical and evolutive study of 122 cases]. / LE purpura rhumatoide de l'enfant : étude clinique et évolutive de 122 cas.

AIM: Analyze the clinical and evolutive particularities of Henoch Schonlein purpura in children METHODS: We studied retrospectively 122 cases enrolled in the pediatrics department of Sousse during 10 years period (1992-2001). RESULTS: It is about 66 boys and 56 girls (sex - ratio= 1.18) aged 3 to 13 years (mean age: 7 years and half). The diagnosis has been established clinically on the presence of cutaneous syndrome with symmetrical declivitous region purpura in all patients with articular syndrome (91cases) and/or digestive syndrome (65cases). Complications were variable: digestive hemorrhage (19 cases), occlusive syndrome (2cases), renal involvement at variable severity (56 cases), scrotal and testicular complications (11 cases), cardiac complications (tamponade in a case). Henoch Schonlein purpura was associated with a primary antiphospholipid syndrome in a case, renal tuberculosis in a case and cholestatic hepatitis A in another case. All patient receeved symptomatic treatment (rest in bed + / - antalgic treatment). Digestive rest was prescribed for 20 patients presenting severe abdominal pains with corticosteroid during 2 at 4 weeks (1-2mg/kg/d) in eight cases. Corticosteroid-cyclophosphamid association was prescribed for 2 patients with severe renal involvement; one of them benefitted of extra-renal purification. One or several relapses of Henoch Schonlein purpura were noted in 13 patients. All sick evolved favorably same those presenting renal or cardiac involvement (middle receding of 5 years).

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.

[Lupus nephritis in childhood: clinical and evolutive study of 14 cases]. / La nephropathie lupique de l'enfant: étude clinique et évolutive de 14 cas.

BACKGROUND: Renal involvement is one of the most severe and frequent manifestations of the systemic lupus erythematosus (SLE). Aim : In this study, we analyzed clinical and evolutive particularities of 14 paediatric cases of lupus nephritis (LN). METHODS: It's a retrospective study in 14 children with lupus nephritis followed-up in the paediatrics department of Sousse and Mahdia between 1983 and 2004. RESULTS: There were 12 girls and two boys (sex-ratio = 0.16) aged four to 14 years (mean age =10 years). At the first presentation, we noted proteinuria in all patients with nephrotic syndrome in six cases, hypertension with variable severity in five cases, hematuria in six cases and a variable severity of renal insufficiency in six cases. Histological examination of kidney performed in 10 patients with severe nephropathy, revealed class IV glomerulonephritis in four cases, class V in two cases and class III in four cases. Thirteen patients were treated by corticosteroids associated with immunosuppressive agent in six cases. One patient had not received any treatment. Five patients were died of the continuations of SLE complications or immunosuppressive therapy. For the other patients, one is in clinical and biological remission since six years, four are lost of view, one is in end stage renal failure, two presented relapsing evolution and one presents refractory form of LN. CONCLUSION: Lupus nephritis is severe in our patients with predominance of class III and IV. New therapeutic strategies permitted to improve the renal survival but at the cost of an important iatrogenic morbidity.

A prospective study of the prevalence of heparin-induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis.

Heparin, which is used at high doses in hemodialysis patients, may induce antibodies favoring thromboembolic complications. We prospectively investigated the prevalence of heparin-induced platelet-reactive antibodies in a cohort of 38 pediatric hemodialysis patients, by means of heparin/platelet factor 4 (H/PF4) ELISA and heparin-induced platelet activation assay (HIPA). We also assessed other acquired and congenital hypercoagulable states. Heparin-induced antibodies were detected in 13 and 21% of patients with HIPA and ELISA, respectively. Anti-H/PF4 antibodies were negatively correlated with the number of hemodialysis sessions. These antibodies disappeared after a median time of 6 months despite continuing heparin treatment. The prevalence of antiphospholipid antibodies was 21% (anticardiolipin 10.5%, anti-beta2GPI 13%, and lupus anticoagulant 5%). Blood levels of homocysteine, factor VIII, and fibrinogen were significantly higher and factor II levels were significantly lower in hemodialysis patients than in controls, whereas factor VII, factor IX, and natural coagulation inhibitor levels were similar in patients and controls. Overall, 26 of 38 patients had at least one biomarker of hypercoagulability, but only 1 patient, without anti-H/PF4 antibodies, presented with thrombosis. In conclusion, heparin induces the transient production of anti-H/PF4 antibodies in children undergoing hemodialysis, but other abnormalities probably contribute to hypercoagulability. These findings may help to improve the diagnosis and management of thrombotic events in hemodialysis patients.

[Mycobacterial infections in children in Central Tunisia. A study of 31 cases including 7 disseminated BCG-osis]. / Infections mycobacteriennes chez l'enfant dans le centre tunisien. Etude de 31 cas dont 7 cas de becegite disseminée.

UNLABELLED: In order to analyze the current epidemiological pattern of mycobacterial infection in children in Central Tunisia, we studied retrospectively the clinical feature of 31 children with mycobacterial infection enrolled in the pediatrics department of Sousse during eight years period (1994-2001). Twenty three boys and eight girls aged two months to 13 years (mean age: 4 years and 8 months) were investigated. Among them, 24 patients suffered of tuberculosis (TBC) and 7 of disseminated BCG-osis. Pleuropulmonary TBC was observed in 12 patients either isolated (7 cases) or in association with at least another localization (5cases). 17 patients had extrapulmonary TBC with variable localisation. The 7 patients with disseminated BCG-osis had an underlying primary immunodeficiency of the cell-mediated immune response. CONCLUSION: The current epidemiology of mycobacterial infections in children in our region indicates a high frequency of severe adverse effects of BCG vaccination occurring in genetically immunodeficient children.

[Clinical features and course of Kawasaki disease in central Tunisia: a study about 14 cases collected over a period of three years (2000-2002)]. / La maladie de Kawasaki au centre Tunisien: aspects cliniques et évolutifs de 14 cas colligés en trois ans (2000-2002).

OBJECTIVE: To analyze the clinical features and course of Kawasaki disease in central Tunisia. We studied retrospectively 14 cases of children with Kawasaki disease collected in tunisian center during three years (2000-2002). The study is about 11 boys and 3 girls (sex - ratio: 3.6/1) aged from 6 months to 8 years (mean age : 4 years). Twelve patients had at least 5 diagnostic criteria of the illness, the two others had an incomplete form. We noted cardiac complications in seven patients treated belatedly, beyond 10 days of progression, because of atypical clinical presentations. All patients had all a middle caliber coronary aneurysm that was complicated by a thrombus in three cases, associated with pericarditis and minimal mitral insufficiency in a case and with a cardiac rhythm disturbance (block of branch) in another case. Besides the cardiac complications, several other visceral manifestation could be noted: joint symptoms in five cases, GI tract symptomes in three cases, neuro-meningeal in two cases and urinary trad symptomes in two other cases. Specific treatment (aspirin with antiinflammatory dose and intravenous immune globulin (IVIG)) has been instituted in all patients. The course was favorable for 12 patients with fast regression of clinical manifestation and progressive normalisation of biologic values. Two patients did not respond to the initial IVIG treatment, and had to recense received an additional course of IGIV but without clinical nor biological improvement. These two patients were treated with corticosteroids. Cardiac lesions disappeared completely in all patients even for those with thrombosis and in patients with IVIG-resistant Kawasaki disease. Only one patient had kept neurologic sequellae: aphasia, bevavioral problemes and partial epilepsy. CONCLUSIONS: Kawasaki disease is not rare in our region. Incomplete or atypical presentations are frequent and are a source of diagnostic delay. Coronary aneurysm due to the delay of treatment often regresses even in patients with IVIG-resistant Kawasaki disease.