F. Kamoun

Hemolytic Anemia and Progressive Neurologic Impairment: Think About Triosephosphate Isomerase Deficiency

We have reported the first Tunisian case of triosephosphate isomerase (TPI) deficiency in a 2-year-old girl. She was the first child of a nonconsanguineous couple. The disease included a neonatal onset of chronic hemolytic anemia, recurrent low-respiratory infections then progressive neurological involvement. The diagnosis was made after her death from the TPI values of her parents who exhibited intermediate enzyme deficiency. Molecular study of TPI genes showed that the father and the mother are heterozygous for Glu105Asp mutation. Pediatricians must be alert to the differential diagnosis in patients having hemolytic anemia and other concomitant manifestations.

Neonatal purulent meningitis in southern Tunisia: Epidemiology, bacteriology, risk factors and prognosis.

Objectives: To study the epidemiological, clinical and bacteriological aspects and outcome of purulent neonatal meningitis (PNM). Methodology: Retrospective analysis of 55 cases of PNM hospitalized in the pediatric ward of Hedi Chaker Hospital from 1990 to 2012. Infants less than 29 days of age were included. The diagnosis was made on either the presence of bacteria in the cerebrospinal fluid (CSF) or the combination of pleocytosis >30 cells/mm3, protein level >1.3 g/l and glucose level <2.2 mmol/l or CSF/blood glucose ratio <0.4. Results: The male:female sex ratio was 1.75. One or more maternal risk factors for infection were found in 24 cases. The main symptoms were fever and poor feeding. Soluble antigen was positive in four cases and cultures had isolated the bacteria in 28 cases. The mortality rate was 40%. The sequelae rate in the survivors was 16.4%. Conclusion: This study emphasizes the severity of PNM with high rates of mortality and neurological sequelae.

Frequent Infections, Hypotonia, and Anemia in a Breastfed Infant.

Vitamin B12 deficiency may be responsible of serious hematologic and neurodevelopmental abnormalities. We report the case of an infant who was hospitalized because of recurrent infections, failure to thrive, hypotonia, and weakness. He was 8 months old and had been exclusively breastfed. Blood cell count showed pancytopenia with megaloblastic bone marrow. The serum IgG concentration was low. Vitamin B12 level was very low and associated with increased urinary methylmalonic acid. Cobalamin deficiency was caused by mother’s unrecognized pernicious anemia. Vitamin B12 supply led to rapid clinical and hematologic improvement.

Clinical and Genetic Characterization of Tunisian Children with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets

Background: Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by the early onset of rickets and is caused by mutations in the vitamin D receptor (VDR) gene. Some HVDRR patients also have alopecia. Patients and Methods: We retrospectively studied the clinical features, laboratory findings, genetic defects, as well as responses to treatment in a series of children with HVDRR. Results: Eight patients from 7 families met the inclusion criteria. Alopecia was noted in 7 patients. Two different homozygous mutations in the VDR gene were identified in 6 patients: the p.K45E mutation located in the DNA-binding domain (5 patients with alopecia) and a novel p.T415R mutation located in the ligand-binding domain. A p.E143del CYP24A1 mutation, in the gene encoding the 25-hydroxyvitamin D3-24-hydroxylase, was identified in 2 brothers carrying the VDR gene mutation p.K45E. Six patients were treated with intermittent intravenous calcium treatment via the peripheral route with a clear improvement in 5 cases. Conclusion: To the best of our knowledge, this is the first major series reporting on HVDRR in Tunisia. The same mutation (p.K45E) was found in 5 apparently unrelated affected individuals. We have also extended the mutation spectrum by studying 1 novel VDR mutation.

Familial haemophagocytosis lymphohisticytosis type 3: A case report

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder of immune regulation. Here, we report on a fatal case of type 3 FHL (FHL3) in a 45-day-old boy. Clinically, the infant presented with fever and hepatosplenomegaly. Biology showed pancytopenia, elevated ferritin, and decreased fibrinogen. Images of hemophagocytosis were found at the bone morrow examination. The diagnosis of FHL type 3 was made by the identification of homozygous mutation in the Munc13-4 gene (UNC13D) located in exon 20: 1822 del 12bp (V608fs). This mutation was previously observed in a Tunisian and in Moroccan families.

Pleurésie à bascule : est-ce une tuberculose ?

Pleural tuberculosis is the first or second most common form of extrapulmonary tuberculosis as well as the main cause of pleural effusion in many countries. It is rare in young infants and is more common in children over 10 years of age. We report the case of a 19-month-old girl admitted for prolonged fever with unilateral pleural effusion. The mother reported a history of lymph node tuberculosis 6 years previously. Intravenous antibiotics with cefotaxime and vancomycin were started. Thoracocentesis yielded a serosanguinous exudate fluid with a lymphocyte predominance. The tuberculin skin test and PCR GeneXpert(©) on pleural fluid were negative. The initial outcome was favorable, but the chest X-rays 10 days after discharge showed bilateral pleural effusion. Pleural biopsy was proposed but the culture of pleural fluid was positive for Mycobacterium tuberculosis. The child was put under standard treatment for tuberculosis. The outcome was favorable.

Chylomicron retention disease: A rare cause of chronic diarrhea.

Chylomicron retention disease (CRD) is a rare autosomal recessive hereditary hypocholesterolemic disorder. The disease most frequently presents in infants and is characterized by a lipid malabsorption syndrome with steatorrhea, chronic diarrhea, and growth retardation. The disease is characterized by normal fasting serum triglyceride levels combined with the absence of apolipoprotein (apo) B48 and chylomicrons after a fat load. In this report, we describe the clinical, laboratory, and histological data as well as the molecular DNA analysis of a 12-month-old girl from Tunisia with CRD. The patient was treated with a low-fat diet and fat-soluble vitamin supplementation resulting in significant improvement.

PO-0106 Sclerosing Cholangitis In Childhood Report Of 3 Cases

Backgrounds and aims Sclerosing cholangitis (SC) is a chronic cholestatic liver disease characterised by inflammation and progressive bile duct fibrosis. Our purpose was to describe characteristics of SC in childhood. Methods We performed a retrospective study of 3 childrens with SC followed in the paediatric department of Sfax (2008–2013). Results There are 2 boys and 1 girl. The mean age at diagnosis was 6 years. Clinical features at presentation were jaundice (1 case) and hepatosplenomegaly (2 cases). Autoantibodies (anti-nuclear antibody, smooth muscle antibody, and perinuclear antineutrophil cytoplasmic antibodies) were detected in 1 case. Magnetic resonance cholangiography revealed irregularities with strictures, dilatations and pruning of bile ducts. Histological examination of liver biopsy showed signs of CS stage I (1 case), stage III (1 case) and portal inflammation with infiltration of lymphocytes and plasmocytes and periductal fibrosis (1case). Search histiocytosis was negative in 3 cases. Colonoscopy with mucosal biopsies revealed no specific inflammatory colitis in one case. The diagnosis of overlap syndrome was made in one case and primary SC (2 cases). All patients were treated with ursodeoxycholic acid and the patient with overlap syndrome received immunosuppressive therapy. After a mean follow-up of 3 years, remission was noted in 2 cases and one patient progressed to cirrhosis and liver failure. Conclusion SC is a rare cause of chronic cholestasis. Ursodesoxycholic acid is the treatment of choice for all forms of SC but without proof of its effectiveness in preventing progression to secondary biliary cirrhosis.

PS-308 Neonatal Bacterial Meningitis In A Developing Country

Background and aims Neonatal bacterial meningitis (NBM) is a serious disease with high morbidity and mortality rates. Aims Study the epidemiological, clinical, bacteriological aspects and the outcome of NBM. Methods We report a retrospective analysis of 55 cases of NBM hospitalised in the paediatric department between 1990 and 2012. Inclusion criteria were infants less than 29 days of age who were hospitalised for bacterial meningitis diagnosed on either the presence of bacteria in cerebrospinal fluid (CSF) or with more than 30 cells/mm3, predominance of neutrophils, the protein level greater than 1.2 g/l and hypoglycorachia. Results The mean age of diagnosis was 11 days and the sex ratio was 1.75. The patients were premature in 9% and low birth weight in 20% of cases. The main circumstances of discovery were fever (69.1%), refusal to breastfeed (49.1%) and seizures (16.4%). A myelomeninguolcele was present in 6 patients. Blood culture was positive in 34.8% of cases and the CSF culture was positive in 54.4% of cases. The main bacteria isolated was Escherichia coli (7 cases), Streptococcus B (7 cases) and Pseudomonas aeruginosa (5 cases). The cefotaximeampicillingentamicin combination was the most prescribed first-line. Ofloxacin was associated initial antibiotic therapy in 9 cases. The mortality rate was 40% and the sequelae rate in survivors was 27%. Conclusion This study emphasises the severity of NBM with high rates of mortality and neurological sequelae. An early diagnosis and effective antibiotic therapy is needed to improve the prognosis.

PO-0166 The Langerhans Cell Histiocytosis In Children: Study Of 11 Cases

Background and aims Langerhans cell histiocytosis (LCH) is a rare disease of unknown cause with manifestations ranging from isolated granulomatous lesions to life-threatening multi-system organ involvement. In this study we aimed to evaluate the characteristics, diagnosis, treatment modalities and prognosis of LCH. Methods We conducted a retrospective study of all cases of LCH in paediatrics department of Hedi Chaker University Hospital in Sfax during a period of 16 years (1997–2013) Epidemiologic, clinical, radiological, diagnostic and therapeutic variables were collected. Results We collected 11 cases of LCH. The average age at diagnosis was 3 years 4 months. The patients’ presenting symptoms were: exophtalmia (3 cases), polyuropolydispsic syndrome (3 cases), prolonged fever (2 cases), lymphadenopathy (5 cases). Laboratory tests showed diabetes insipidus (3 cases) and bicytopenia (1 case). The diagnosis was confirmed by histopathologic examination in all cases. Bone was the most frequently affected organ (9 cases) followed by skin (19.2%). Initially, 4 patients had single-system involvement (SS), 3 with mulisystem (MS) disease without risk organ involvement (MS-RO), and 4 multisystem disease with risk organ involvement (MS-RO). Chemotherapy based on vinblastine with corticosteroids was used in 4 patients who had MS-RO form. The outcome was favourable in 6 cases. Conclusions Langerhans cell histiocytosis is a rare and heterogeneous disease. Multisystem disease with risk organ involvement justify the use of many drugs.