[Cystic fibrosis: a report of 33 pediatric Tunisian cases]

Background: The frequency of cystic fibrosis is unknown in Tunisia, regarding the limited number of reported surveys and patients

Aim: to determine the clinical characteristics, outcome and genetic data of cystic fibrosis in Tunisian pediatric patients

Methods: Cases of cystic fibrosis managed at pediatric departments of Tunis, during 15 years [1997-2012], were reviewed

Results:33 children [23 males and 10 females] were enrolled. The Onset was within the first year of life in 26 patients. Revealing symptoms were the following: recurrent bronchopneumonia [28 cases], chronic diarrhea [17 cases], hepatomegaly [6 cases], malnutrition [15 cases], pseudo Bartter syndrome [3 cases], edemaanemia- hypoprotidemia [4 cases] and meconium ileus [4 cases]. The diagnosis was confirmed by sweat test and genotypic data, the F508 del was the most frequent mutation [17 cases]. Several complications had occurred during follow-up: chronic pseudomonas aeruginosa infection [15 cases], chronic respiratory failure [14 cases], recurrent hemoptysis [2 cases], pleural effusion [3 cases] and cirrhosis [2 cases]. Ten patients died at a mean age of 7 years. One patient had pulmonary transplantation. Prenatal diagnosis was performed in 9 families

Conclusion: In Tunisia, cystic fibrosis is not exceptional, but its diagnosis is delayed. Our survey is characterized by more severe earliest forms, difficult and insufficient therapeutic management. A Better medical awareness and a national action plan are needed

[Neuroacanthocytosis: a diagnosis that should be considered]

Neuroacanthocythosis regroup heterogeneous neurodegenerative diseases. These conditions share neurological, hematological and even systemic features. In spite of the genetic progress, their pathogenesis is still unknown. To report a new case of neuroacanthocythosis. A 37-year-old woman was admitted for orofacial choreatic movement disorder. These movements were associated to dysarthria, lip and tongue mutilation, areflexia and raised plasma creatine kinase level. Examination of blood smear reveled 10% of acanthocytosis. Neuro-acanthocytosis diagnosis, precisely chorea-acanthocytosis, was done. Neuro-acanthocytosis should be considered in any movement disorder in order to attempt a genetic counseling

[ 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

[Liver involvement in Gaucher's disease: a tunisian cohort study]

Gaucher disease is a sphingolipidosis related to glucocerebroside storage in reticuloendothelial cells leading to multisystemic disease. Liver involvement is frequent but clinical expression is rare. The aim of this study is to evaluate liver involvement among a cohort of 45 patients with type 1 Gaucher disease. Hepatomegaly often mild to moderate was seen in 86 per cent of cases. A correlation was noted between hepatic involvement, spleen enlargement and severity index score. Portal hypertension was documented in 20 per cent of cases and seemed to be primitive. Four children had cirrhosis and two a hepatopulmonary syndrome. Splenectomised patient didn't show worsening of liver involvement. Liver complications were more frequent in pediatric patients comparatively to adult patients in this cohort

[Phenotypic spectrum of zellweger syndrome about three cases]

Peroxisome biogenesis disorders associate the spectrum of Zellweger syndrome and Rhizomelic chondrodysplasy. We have studied two cases of Zellweger syndrome and a case of neonatal adrenoleucodystrohpy. Clinical picture consisted with neonatal hypotonia with seizures in all cases, facial dysmorphia in two cases and a punctata chondrodysplasia in one case. Deafness and blindness were found in two cases. Cerebral tomography revealed white matter hypodensities in all cases. The diagnosis of Zellweger syndrome was enhanced by high level of plasmatic very-long-chain fatty acids and deficiency of DHAP-AT activity and b oxidation of C26:0 in fibroblasts. Ultrastructural studies showed peroxisomal ghosts in one patient. Genetic analysis detected a punctual mutation on PEX 26 gene. The prognosis was poor with the death of the two Zellweger at the age of 9 month with resistant seizures, and at the age of 4 years for the ALD. The prenatal diagnosis was performed in one family

[Singular etiology of inherited aplastlc anemia: a case report of congenital dyskeratosis]

Congenital Dyskeratosis [CD] is a severe inherited disease characterised by a triad of clinical manifestations including abnormal skin pigmentation, nail dystrophy and mucosal leucoplakia. Other clinical manifestations including lung fibrosis and liver cirrhosis worsen the prognosis. Bone marrow hypoplasia is frequently reported, 50 per cent of patients develop pancytopenia before the age of 10 years. We report here the first Tunisian case of DC diagnosed in paediatric age and revealed by a severe bone marrow failure by the age of ten years. The classic triad appeared in the first decade, epiphora, blepharitis, teeth abnormalities and a single kidney were also noted. Androgen therapy stabilised peripheral cytopenia and, decreased the need of red blood cell transfusion

[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

Deficiency in complex IV of mitochondria respiratory chain

Mitochondrial cytopathies are diseases due to a defect of mitochondrial respiratory chain and are characterized by the presence of morphological abnormalities of mitochondria. These diseases may be due to alterations of the mitochondrial or the nuclear genome. The clinical manifestations can be polymorphic as various organs may be involved. We report the case of a 2-year-old boy who has a declined development correlated with a distal renal tubular acidosis. His behavioural and motor development was normal until l2months when a regression of his motor milestones with a pyramidal syndrome was noted. The metabolic investigation and the cranial MRI revealed a Leigh syndrome. The biochemical and immunological studies on biopsied skeletal muscle and cultured skin fibroblasts showed a deficiency in the complex IV respiratory chain [cytochrome c oxidase or COX]

[Hyperlipemia and lymphoma]

While the concept of developing hypocholesterolemia during myeloma or lymphoma is not unusual, the existence of developing hyperlipemia is rare. The authors report the case of a sixty-one year old diabetic patient treated by oral medication. This patient does not have a family history of hyperlipemia. He was hospitalized for degradation of his general condition, and a pain of the right shoulder and bilateral pleural effusion. A major hyperlipidemia [total cholesterol = 13.5 mmol/l, triglycerides = 16.8 mmol/l] was noted during his hospitalization and persisted in spite of a fibrate treatment and a controlled diabetes. The radiography of the upper right limb showed lytic images of the extremity of the humerus. The thoracic CT scan showed bilateral pleural effusion and a hyperdense paravertebral image of ganglion metastasis. The myelograme and the pleural biopsies showed a malignant non hodgkin lymphoma. An immunosuppressor treatment was prescribed resulting in a spectacular improvement of the hyperlipidemia since the first chemotherapy. This is probably an autoimmune hyperlipidemia associated with a lymphoma. Further investigations like the study of the lipoprotein lipase activity, the search of antibodies related to the apo E or the apo B would be useful in order to confirm this assumption