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.

Diabetic acido-ketosis revealing thiamine-responsive megaloblastic anemia.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder characterized by megaloblastic anemia, diabetes mellitus and progressive sensorineural deafness. We report the cases of two infants, aged 4 and 5 months, hospitalized for diabetic ketoacidosis requiring insulin therapy. Laboratory tests revealed megaloblasic anemia, thrombocytopenia and normal thiamine level. Neurosensorial investigations showed bilateral deafness and ophthalmic involvement. Treatment with oral thiamine normalized hematological disorders and controlled diabetes; however, thiamine therapy had no impact on neurosensorial disorders.

[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.

[Clinical and etiological features of primary adrenal insufficiencies in children]. / Aspects cliniques et etiologiques de la maladie d'Addison chez l'enfant.

BACKGROUND: The chronic primary adrenal insufficiency or Addison's disease is uncommon in children and belongs generally to a complex syndrome. AIM: Study of the clinical and aetiological features of primary adrenal insufficiencies in children. METHODS: In a retrospective study, we reviewed clinical and diagnostic data of all cases of Addison's disease admitted within a period of 15 years (from january 1991 to December 2006), in a department of paediatrics. Cases due to congenital adrenal hyperplasia were excluded. RESULTS: 6 cases of Addison's disease were diagnosed. Five patients are the product of consanguineous marriage. The age at the diagnosis of adrenal insufficiency varried from 15 months to 9 years 8 months. The adrenal insufficiency was associated to Allgrove syndrome in three cases, to autoimmune polyendocrinopathy type 1 in one patient and to probable peroxisomal disease in another one. The etiological disease was not determined in one patient. A substitutive hormonal therapy was conducted in all patients. During a mean follow-up of 26 months, two adrenal crises were noted. CONCLUSION: Larger studies about Addison's disease are needed to confirm the preponderance of the Allgrove syndrome.

[Cardiotoxicity of n-methyl-glucamine antimoniate (Glucantime). A case report]. / Toxicité cardiaque de l'antimoniate de méglumine (Glucantime). A propos d'une observation.

The pentavalent antimonial meglumine (Glucantime) is the drug of choice in treatment of cutaneous leishmaniasis in Tunisia. It may create severe adverse effects. A ten year-old girl was treated by Glucantime for cutaneous leishmaniasis. On the eighth day of treatment, she developed palpitations and precordialgia. The ECG showed T wave inversion prolongation of corrected QT interval. Drug therapy was stopped. Within a few days, she recovered and her elctrocardiographic changes came back to normal. The cardio toxicity of Glucantime may be severe. Electrocardiographic changes are the primary signs. Long term ECG follow-up is necessary.

[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.