Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations.

[Pediatric Crohn's disease in Tunisia]. / La maladie de Crohn de l'enfant en Tunisie.

UNLABELLED: Crohn's disease occur mainly in adults. However, pediatric onset forms are not rare and have many characteristics. AIM: to study clinical, diagnostic, therapeutic and evolutive characteristics of crohn's disease in tunisian children. METHODS: Retrospective multicenter study conducted in 10 pediatric departments on a period of 10 years (2000-2008) RESULTS : 43 children were included. The sex-ratio was 1.68. The mean age at the onset of the symptoms was 11+/-2.3 years (5-16 years). The age of onset was inferior to 10 years in 25 % of the children. The delay before management was superior to 1 year in 25% of cases. The initial symptoms were dominated by diarrhea (95%). Perineal manifestations were present at diagnosis in 30% of children and extra-digestive manifestations in 53%. Ileocolonic localization was the most frequent (46%). The initial disease flare was moderate in 83% of cases. The treatment was medical in 77 % of cases, nutritional and medical in 18.5%. Maintenance therapy was instituted in 86% of cases and consisted essentially in azathioprin (62%). The mean follow-up was 3 years and 4 months. 60% of the children had at least one acute flare. During evolution, 7% of children had anoperineal surgery and 11% an intestinal resection. CONCLUSION: Crohn's disease seems rare in Tunisia. The time of diagnosis is often delayed. The management is based on immunosuppressive therapy and nutritional support.

[The re-emergence of pertussis in Tunisia]. / La réémergence de la coqueluche en Tunisie.

OBJECTIVE: The authors had for aim to analyze pertussis epidemiology in Tunisia by studying nasopharyngeal specimens of infants hospitalized in Tunis. METHODS: Between march 2007 and march 2008, clinical nasopharyngeal samples were collected from infants with a suspected diagnosis of whooping cough, pertussoid cough, or pertussis-like syndrome, admitted at the Tunis children's hospital. The laboratory diagnostic criteria were culture isolation of Bordetella species on Bordet-Gengou medium and real-time PCR. RESULTS: Fifty-nine percent of the 74 investigated children with suspected pertussis were less than two months of age. The diagnosis of pertussis was proved positive by real-time PCR for 41%. Culture was negative in all cases. CONCLUSIONS: Whooping cough is still prevalent in Tunisia despite an important vaccination coverage. Real-time PCR is an invaluable tool for the rapid diagnosis of pertussis, however culture must also be associated.

[Use of the rapid antigen detection test in group A streptococci pharyngitis diagnosis in Tunis, Tunisia]. / Utilisation d'un test de diagnostic rapide des angines à streptocoque bêta-hémolytique du groupe A, auprès d'un échantillon d'enfants à Tunis, Tunisie.

The aims of this study were to determine the contribution of commercial rapid antigen detection test (RADT) in the rapid diagnosis of pharyngitis caused by group A streptococci. A total of 292 children with pharyngitis was included. A duplicate throat swabs was taken simultaneously from each patient. One of them was used for RADT achievement and the other for culture. When cultures were positive, a semi-quantitative evaluation was done. Throat culture and RADT were positive in 59 and 72 cases respectively. Fifty four specimens were positive simultaneously with RADT and culture and 215 specimens were negative using both methods. Eighteen specimens were positive only with RADT, 5 of them were treated by amoxicillin. Regarding to the group of patients with a negative RADT and a positive culture (5 cases), all of them had a culture evaluation at "+" or "++". Specificity and sensibility of the RADT were 92.2% and 91.5% respectively. RADT use by physicians can reduce antibiotic prescription among paediatric population. Because of the high specificity of RADT, therapeutic decisions can be made on the basis of a positive test.

[Central diabetes insipidus: diagnostic difficulties]. / Diabète insipide central: difficultés diagnostiques.

UNLABELLED: Central diabetes insipidus is rare in children. Characteristic features include polyuria and polydipsia due to arginine vasopressin deficiency. The differential diagnosis of polyuric states may be difficult. Etiologic diagnosis of central diabetes insipidus may be an equally difficult task. OBJECTIVE: To specify the difficulties encountered in the diagnosis of central diabetes insipidus and to point out features of the etiologic work-up and of long-term follow-up of children with idiopathic central diabetes insipidus. METHODS: A retrospective study of 12 children admitted with a polyuria/polydipsia syndrome to the pediatric - consultation and emergency unit of the children's hospital of Tunis between 1988 and 2005. Children with acquired nephrogenic central diabetes insipidus were excluded. Fourteen-hour fluid restriction test and/or desmopressin test were used without plasma vasopressin measurement. RESULTS: Eight patients were classified as having central diabetes insipidus, which was severe in seven children and partial in one girl. One patient was classified as having primary polydipsia. The diagnosis remains unclear in three patients. The etiological work-up in eight patients with central diabetes insipidus enabled the identification of Langerhan's-cell histiocytosis in two patients and neurosurgical trauma in one. The cause was considered idiopathic in five patients. The median follow-up of the five patients with idiopathic central diabetes insipidus was five years two months plus or minus six years seven months (range five months, 14.5 years). During this follow-up, neither brain magnetic resonance imaging scans findings nor anterior pituitary function have changed. CONCLUSION: Fluid restriction and desmopressin tests did not enable an accurate distinction between partial diabetes insipidus and primary polydipsia. Regular surveillance is warranted in patients with idiopathic central diabetes insipidus to identify potential etiologies.

[Currarino syndrome a rare cause of recurrent purulent meningitis]. / Syndrome de Currarino cause rare de méningites purulentes récidivantes.

The authors report a case of partial Currarino syndrome in a three and a half year old child with a left hemisacrum agenesis and a presacral mature teratoma. The special aspect of the observation was the apparition of repetitive polymicrobial purulent meningitis (Escherichia coli, Streptococcus B, Haemophilus influenzae) treated several times with non-specific antibiotics without normalization of CSF, particularly the CSF glucose, which remained low, justifying the use of an antimycobacterial treatment, especially since there was no local or general cause explaining the relapse. During a relapse of meningitis after ten months of antituberculosis treatment, the teratoma was discovered by a spine MRI done to detect any cerebrospinal defect. The authors insist on the fact that the Currarino syndrome must be investigated in case of repetitive purulent meningitis after ruling out the usual causes of meningitis.

[Uveitis of children: a report of 18 cases]. / Les uvéites de l'enfant: étude de 18 observations.

UNLABELLED: Childhood uveitis is a rare but serious disease that may causes visual loss. Causes are various and an underlying disease is not always found. PURPOSE: To analyse clinical features and prognosis of uveitis in children. PATIENTS AND METHODS: A retrospective, descriptive study of cases observed in a general pediatric unit over a period of 15 years (1990-2005) at Tunis. RESULTS: We gathered 18 cases of uveitis (girls 55.6% ,boys 44.4%). Mean age at the diagnosis was 8+/-3 years. Diagnosis was made after a decreased of visual acuity in 55.6% of cases. Localization of uveitis was anterior (6 cases), intermediate (1 case), posterior (3 cases) and total (8 cases). An underlying disease was found in only 5 patients: Behçet's disease (3 patients), juvenile chronic arthritis (1 patient), possible dermatopolymyositis (1 patient). The evolution was favorable in 10 cases with local treatment, systemic corticotherapy and/or immunosuppressive agents. Complications occurred in 3 cases. CONCLUSION: Causes of uveitis in childhood remains most often undiagnosed Our study illustrates the pending risk of severe visual impairment and strict ophtalmology follow-up is mandatory.

[Arabian variant of Kenny syndrome: a familial case in Tunisia]. / Variant arabe du syndrome de Kenny: à propos d'une famille maghrébine.

Kenny syndrome is rare. Clinical feature include severe dwarfism, growth retardation macrocephaly, episodic hypocalcemia, internal cortical thickening and medullary stenosis of tubular bones. Genetic and phenotypic polymorphisms are characteristic. We report the observation of a Tunisian girl with the arabic variant of Kenny syndrome. She had chronic hypoparathyroidism, classic dwarfism, short stature with hormone deficiency, mental retardation and low helper/suppressor ratio. Our patient had two sisters and one brother with the same dysmorphic face and a marked intra-uterine growth retardation. They died from severe infections. Hypoparathyroidism was established in one sister.

[Gaucher's disease in Tunisia (multicenter study)]. / La maladie de Gaucher en Tunisie (étude multicentrique).

UNLABELLED: Gaucher's disease is one of the rare lysosomial disease that could receive substitutive enzymatic treatment which may improve considerably the prognosis of certain forms. The purpose of this work is to study the epidemiology of the disease in Tunisia, to highlight the diagnostic and therapeutic difficulties and also to precise our subsequent needs for substitutive medication. PATIENTS AND METHODS: We have conducted a retrospective survey of the hospital wards that were susceptible to take care of patients having Gaucher's disease. These wards are the paediatric, neonatology, internal medicine, haematology, neurology and cardiology wards. RESULTS: In this study we have observed 27 cases of Gaucher's disease over a period of 18 years (1983-2001). The age at onset ranges from birth to 73 years of age, with an average age of 14.5 years. According to the age at onset and the clinical presentation, we classify our patients into: 20 cases of type 1 (74%), three cases of type 2 (12%), and three cases of type 3 (12%), and one case of unspecified type.Gaucher's disease type 1: The age at onset ranged from 10 months to 73 years with an average of 19 years. The main clinical signs that we have observed were splenomegaly, hepatomegaly, pallor, haemorrhagic appearance and also osteoporosis and bone pain observed in 40% of the cases. The diagnosis was based on histology showing the Gaucher's cells in various tissues while the diagnosis obtained by the dosage of glucocerebrosidase took place only in 50% of the cases. The treatment has always been symptomatic (analgesics, transfusion). A splenectomy was performed in 47% of the cases and none of the patients received a specific treatment. The follow-up period ranged from 1 month to 18 years with an average follow-up of 4 years. Among the 12 patients having a follow-up of at least 1 year, we have noticed an improvement after splenectomy in three cases, a stability in three cases and two worsening cases dealing mainly with bone problems. One patient aged 73 died from respiratory problem and three were lost to follow-up. Gaucher's disease type 2: We have observed three cases of Gaucher's disease type 2 diagnosed at 1 day, 45 days and 3 months of age. The visceral manifestations were serious and the neurological features included seizures, hypertony, ocular-nerve palsies and psychometric decline. The three patients died. Gaucher's disease type 3: Three patients were probably suffering from Gaucher's disease type 3 with visceral manifestations observed at the ages of 9 months, 1 year and 3 years, and also neurological signs observed at respective ages of 2.5 and 3 years. Two patients died and the remaining one was lost to follow-up. CONCLUSION: Gaucher's disease is not exceptional in Tunisia. Type 1 is by far the most common one. We have noticed some insufficiency in the diagnosis as the glucocerebrosidase enzymatic dosage was performed only in 50% of the cases as well as therapeutic insufficiency with no prescription of the specific treatment.

[Visceral leishmaniasis in immunocompetent children: diagnostic and epidemiologic value of peripheral leishmania blood culture]. / La leishmaniose viscérale, de l'enfant immunocompétent: intérêt diagnostique et épidémiologique de la recherche des leishmanies par culture du sang périphérique.

Utilisation of new diagnosis means and particularly non invasive oues in visceral leishmaniasis can be very valuable for the biologist, the clinician as well as the patient. In this, detection of leishmania in peripheral blood, well know for VIH patients, has been applied to 37 immunocompetent tunisan children suffering from kala azar that has been shown through direct examination of bone marrow. Observed results show that culture on NNN peripheral blood medium was positive in 25 cases (67.57%). On the other side, detection of leishmania through concomitant culture of blood and marrow bone for 24 children with visceral leishmaniasis match the results in 75% of the cases. Detection of leishmania by mean of blood culture for immunocompetent children is a diagnosis mean of visceral leishmaniasis and has also an epidemiologic utility by isoenzymatic characterization of isolated leishmania strains.

Childhood diabetic neuropathy: a clinical and electrophysiological study.

Clinical diabetic neuropathy in childhood is rare, but electrophysiological involvement of the peripheral nerve is more frequent. We assessed clinically and electrophysiologically the peripheral nervous system of 69 children and adolescents suffering from diabetes mellitus (DM). The mean age of the patients was 12.8 years and the mean age at onset of DM was 6.8 years with a mean disease duration of 6.3 years. Seven patients (10%) had clinical neuropathy of which ankle jerk reflex abolition was the most frequent sign. Twenty patients (29%) had a neurophysiological neuropathy prevalently affecting the lower limbs. Peripheral neuropathy was correlated with patient age, older age at onset, duration of DM, height and poor glycaemic control.

[Sydenham's chorea in children]. / Chorée de Sydenham chez l'enfant.

BACKGROUND: Sydenham's chorea was the most common form of acquired chorea in childhood. Its incidence has declined since the use of antibiotics. The aim of our study was to determine the hospital incidence of this disease and to illustrate the clinical characteristics and outcome of this disease in Tunisia. POPULATION: Retrospective study of 15 cases of Sydenham's chorea, seen between 1987 and 1997. RESULTS: Our patients (five boys and ten girls) represented 5.6 per 1000 hospitalized children. Their mean age was 10.5 years. Two patients had a history of rheumatic fever and five had a history of throat infection during the month before chorea. The onset of symptoms was acute in five cases and insidious in ten. Choreic movements were generalized but asymmetrical in 12 cases, and unilateral in three. Psychological disorders were noted in nine cases and hypotonia in six. Rheumatic carditis was found in three patients. No patient had an obvious increase in sedimentation rate, and antistreptolysin were increased in 50% of cases. All patients were given haloperidol and five steroids, 11 were given antibiotics at the attack of chorea and 13 received secondary prevention with benzathine penicillin. Initially, abnormal movements disappeared in all cases after a mean of three months. Three patients relapsed and two among them still show abnormal movements and psychological disorders after a follow-up of 3 and 3.5 years respectively. CONCLUSION: Sydenham's chorea, although less frequent than previously, is not exceptional in Tunisia. Malignant forms are not observed, but two of 15 patients developed a chronic form with sequelae. No correlation is found between outcome and secondary prevention of streptococcal infections.

[Cerebral hydatic cysts in children]. / Les kystes hydatiques cérébraux chez l'enfant.

BACKGROUND: Brain cysts caused by Echinococcus granulosus are rare; they occur during childhood in endemic areas. PATIENTS: Six children, aged to 8.5-years old (mean age: 5.5 years) were admitted from 1989 to 1994 because they suffered from progressive intracranial hypertension. The brain CT-scan showed typical features of supratentorial, unilocular (four cases) or multilocular (two cases) cysts. Three children had positive serological test; two had another cyst into their lung or liver and the third had generalized cysts. This last patient died post-operatively while the five others recovered after excision of cysts. CONCLUSION: Any progressive intracranial hypertension in endemic areas requires brain CT-scan that clearly identifies the cyst and its location.

[CHARGE association]. / Association CHARGE.

BACKGROUND: The spectrum of CHARGE association includes coloboma, heart disease, choanal atresia, retarded growth and development and/or CNS anomalies, genital anomalies and/or hypogonadism and ear anomalies and/or deafness. CASE REPORT: A 4 1/2 month-old boy was admitted suffering from microphthalmia. His weight was 6 kg (-1 SD), height 60 cm (-2 SD) and his head circumference was 44 cm (+ 2 SD). He had hypotonia. Examination showed low-set ears, micrognathia, coloboma, left choanal atresia and genital hypoplasia. His heart was normal. CONCLUSION: The CHARGE association must be recognized early since it may be complicated by respiratory and feeding difficulties which can be lethal.