Congenital chloride diarrhea in two yemeni siblings

Congenital chloride diarrhea [CCD] is a rare disorder caused by a genetic defect in the chloride/bicarbonate exchange in the ileum and colon which manifests as a neonatal secretory diarrhea with electrolytes imbalance and predispose to long-term complications. The disease is highly prevalent in the Arabian Peninsula. We report two Yemeni siblings with CCD. Family history was significant with two deaths at 3 months of age. Polyhydramnios, antenatal dilated bowels, prematurity and neonatal onset of watery diarrhea were found in both infants. As a result of inadequate electrolytes supplementation, both children had growth development retardation and one developed a chronic renal disease at 6 years of age

[ novel mutation in PEX 26 gene in Zellweger syndrome: a case report]

Zellweger syndrome is the most severe phenotype of the peroxisome biogenesis disorders caused by mutations in PEX genes. PEX 1, 6 and 26 genes are most frequently implicated. Clinical phenotype can't predict the mutated gene. To report a novel mutation in the PEX 26 gene in infant with typical Zellweger syndrome. The infant was the second child to consanguineous parents; the 1st child was dead with neonatal hypotonia. At two month of age, we noted a severe hypotonia and growth failure, characteristic facial dysmorphic features and cryptorchidism. Sensorial investigations showed optic atrophy. Cerebral tomography revealed white matter hypodensity. Radiological examination revealed calcific stippling of the patellas. The clinical diagnosis was supported by measurement of plasma very-long-chain fatty acids, with elevated C24:0/C22:0, C26:0/C22:0 ratios and decreased docosanoic acid peak. The diagnosis was confirmed by dosage of DHAP-AT activity in fibroblasts which was very low. Ultrastructural examinations showed the presence of peroxisomal ghosts. Genetic analysis demonstrated a new mutation in PEX 26 gene.The death occurred at the age of 8 months of refractor epilepsy and apneas. The poor prognosis of ZS incites paediatricians to consider this disorder in etiological investigations of precocious hypotonia. Biochemical diagnosis, available in Tunisia, offers opportunity of prenatal diagnosis in affected families

[Congenital Hyperinsulinism: review of 12 Tunisian cases]

Congenital hyperinsulinism in infancy [CHI] is a heterogeneous disorder with respect to genetics and response to therapy. Data on CHI are sporadic in North African population. To characterize the clinical features and outcome of 12 Tunisian patients with CHI. data of patients diagnosed with CHI during the period 1989-2007 were retrospectively analyzed. Diagnosis was considered whenever hyperinsulinemia 10 UI/ml was concomitant to hypoglycemia<3mmol/l and/or high insulin to glucose ratio>0.3 and/or positif glucagon test. Transient causes of hypoglycemia, adrenal and growth hormone deficiency were excluded. There were nine infants diagnosed at a median age of 17 months and three newborns. Permanent hyperammoniemia, found in one patient, guided to leucine-sensitive hyperinsulinism. Seven patients presented with seizures, two with psychomotor delay and one with recurrent malaises. Among 42 assays of plasmatic insulin, when in hypoglycemia, 40% only were 10 U/ml. Three patients resisted to diazoxide and underwent subtotal pancreatectomy complicated by diabetes mellitus in two cases and persistent hypoglycemia in one patient. Histological examination concluded to diffuse hyperplasia of pancreatic cells. Diazoxide was discontinued in four out the eight responders patients. Four patients died, seven patients developed variable degrees of mental retardation and five suffered from epilepsy. Early onset forms were, as reported in the literature, mostly resistant to medical therapy. The high proportion of neurological sequelae is related to diagnosis delay or to a late surgery. We focus on the importance of a precocious diagnosis and aggressive treatment of hypoglycemia

[Roasai- Dorfman disease: a two cases report]

Rosai-Dorfman disease [RDD] is a benign lymphoproliferatif disorder characterized by cervical lymphadenopathies with a consistent risk of airways' compression and esthetical prejudice. Extra nodal localizations are also described. To report two pediatric cases of RDD. The first case concerned a patient with a prolonged nodal involvement of RDD. Remission seems to be natural although it coincided with a sulfam‚thoxazole- trim‚thoprime therapy. The second case illustrated an extranodal form of RDD localized in soft tissue and paranasal sinus with extension to nasal cavity which were corticodependant. RDD is usually a benign disorder. Particular localizations, lack of effective therapy and the high risk of recurrence are important issues in this rare affection

Phenotype and mutational spectrum in Tunisian pediatric Gaucher disease

Gaucher disease [GD] is a sphingolipidosis with heterogeneous phenotypic expression. The vital and/or functional prognosis maybe threatened by an early visceral severe inolvement 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 study is to highlight the specific phenotypic and genotypic changing among the widest Gaucher pediatric cohort in the Tunisian population. A restrospective study of a sample of children involved by gaucher disease. 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 1GD. 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 2GD 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 RecNcil mutations seem to occur more frequently compared to the GD forms presenting in adulthood. 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]

The mucopolysaccharidoses [MPS] are a devastating heterogenous group of lysosomal storage disorders. 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. 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. The reported frequency of all types of MPS in Tunisia is underestimated

[Enzyme replacement therapy for gaucher pardiatric disease: the only Tunisian Experience]

We report through the first Tunisian experience with enzyme replacement therapy, the goals and consensus recommendations for treatment and monitoring of paediatric non neuronopathic Gaucher disease. Three children with Gaucher disease undergone enzyme replacement therapy with Cerezyme for severe visceral and/or bone involvement. Visceral, hematologic, bone, and growth parameters were assessed initially and under treatment. Two children presented with severe visceral or hematologic picture. One patient had myocardiopathy and primitive portal hypertension and another was diagnosed with cirrhosis related to Gaucher disease. Recurrent avascular necrosis and osteoporosis have justified treatment in another child. All patients received an initial dose of 60U/Kg/2 weeks. We have seen a gradual disappearance of hepatosplenomegaly and a rapid normalisation of hematological parameters in two patients. A resistance to treatment indicated splenectomy in one patient. The improvement in bone mineral density was slower. A significant growth gain was observed in patients with growth retardation. No patient had developed Cerezyme antibodies. Despite its effectiveness and safety demonstrated in these children, enzyme replacement therapy remains inaccessible because of its cost for emerging countries. The allogeneic bone marrow is an alternative therapy to encourage and to propose precociously for severe paediatric forms of Gaucher disease