[Rheumatic cardiopathies and its risk factors: about 50 cases]. / Les complications cardiaques du rhumatisme articulaire aigu et ses facteurs de risque : étude de 50 observations.

INTRODUCTION: Acute rheumatic fever (ARF) is a multi-systemic disease, in which cardiac involvement is the most serious major manifestation of disease. The aim of this study was to analyse cardiac involvement in children with ARF and his risk factors. MATERIALS AND METHODS: It were a retrospective study including all children under the age of 14 years who were hospitalized for ARF in the pediatric department of the CHU Hédi Chaker of Sfax, during a period of twelve years (2010-2022). RESULTS: We collected 50 cases (31 boys and 19 girls). Twenty-two patients (44%) developed cardiac lesions. The mean age at diagnosis was 9.6 years [5-14 years]. A pathological heart murmur was detected in 14 cases (n = 14/22) was classified as mild carditis in 15 cases, moderate carditis in 5 cases and severe in 2 cases. The median follow-up time was 3,3 years. Nineteen patients developed valvular sequelae Risk factors of cardiac lesions was: age more than 8 years, heart murmur, allonged PR, CRP > 100 mg/l and VS > 100 mm. CONCLUSION: CR is still a public health problem in Tunisia. It is a serious pathology that can cause serious increases in morbidity rates. Thus, we must strengthen preventive strategies.

Vitamin B1 deficiency leads to high oxidative stress and mtDNA depletion caused by SLC19A3 mutation in consanguineous family with Leigh syndrome.

Leigh syndrome (LS) and Leigh-like spectrum are the most common infantile mitochondrial disorders characterized by heterogeneous neurologic and metabolic manifestations. Pathogenic variants in SLC carriers are frequently reported in LS given their important role in transporting various solutes across the blood-brain barrier. SLC19A3 (THTR2) is one of these carriers transporting vitamin-B1 (vitB1, thiamine) into the cell. Targeted NGS of nuclear genes involved in mitochondrial diseases was performed in a patient belonging to a consanguineous Tunisian family with LS and revealed a homozygous c.1264 A > G (p.T422A) variant in SLC19A3. Molecular docking revealed that the p.T422A aa change is located at a key position interacting with vitB1 and causes conformational changes compromising vitB1 import. We further disclosed decreased plasma antioxidant activities of CAT, SOD and GSH enzymes, and a 42% decrease of the mtDNA copy number in patient blood.Altogether, our results disclose that the c.1264 A > G (p.T422A) variant in SLC19A3 affects vitB1 transport, induces a mtDNA depletion and reduces the expression level of oxidative stress enzymes, altogether contributing to the LS phenotype of the patient.

Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT).

OBJECTIVES: Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls. METHODS: Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments. RESULTS: We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4 %) with mosaicism in 37(20 %). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3 %), from birth-2 years in 14 (8 %)with lymphoedema (8)and dysmorphic features (9),2-12 years in 53 (35.5 %) including 35 with short stature, 13-18 years in 43(28.8 %) with short stature(28) and delayed puberty(14) and 35(23.5 %) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8 %), renal in 22 (19.6 %). A total of 56 girls (32 %) had proven gonadal dysgenesis and 13 (7 %) had otological problems. Parental height was available in 71 girls (40 %) of whom 59 were below the lower end of parental target range (LTR) (83 %). CONCLUSIONS: This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years' time.

Precocious Pseudo-puberty in a Two-year-old Girl, Presenting with Bilateral Ovarian Enlargement and Progressing to Unilateral Juvenile Granulosa Cell Tumour

Ovarian causes of precocious pseudo-puberty (PPP) include McCune-Albright syndrome (MAS) and juvenile granulosa cell tumour (JGCT). We describe a case of PPP in which bilateral ovarian enlargement with multiple cysts progressed to unilateral JGCT. A girl aged 2.17 years presented with three months of breast development, and rapid growth. Examination showed tall stature, height +2.6 standard deviations, Tanner stage B3P2A1. A single café au lait patch was noted. Bone age was advanced at 5 years. Pelvic ultrasound showed bilaterally enlarged ovaries (estimated volumes 76 mL on the left, 139 mL on the right), each containing multiple cysts. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) values before/after gonadotrophin administration were 0.43/0.18 and <0.1/<0.1 mUI/mL, serum estradiol 130 pg/mL, (prepubertal range <20 pg/mL). PPP of ovarian origin was diagnosed, and tamoxifen 20 mg daily started. However, after only seven weeks height velocity escalated and breast development increased to B3-4 with menorrhagia. Basal/stimulated LH and FSH were still suppressed at 0.13/0.25 and <0.1/<0.1 mUI/mL and, serum estradiol 184 pg/mL. Repeat imaging now showed normal right ovary (volume 1.8 mL) and a large left-sided vascular solid/cystic ovarian tumour which was excised (weight 850 g). Histology showed JGCT, International Federation of Gynecology and Obstetrics stage IA. DNA from tumour tissue showed no mutation in GNAS, exon 3 of AKT1 (which contains a mutational hotspot) or FOXL2. The observation that bilateral ovarian activity progressed to unilateral development of JGCT in this patient is novel. This case highlights current uncertainties in the ontology of JGCT, and its possible relationship with MAS.

Congenital lung malformations : analysis of 27 cases.

INTRODUCTION: Congenital lung malformations (CLM) include a complex range of developmental abnormalities. Currently, most are diagnosed prenatally or during early childhood. OBJECTIVE: to investigate clinical and imaging findings of congenital lung malformations in children. METHODS: Retrospective study of CLM diagnosed between 2000 and 2017 at the pediatric and neonatology department of Hedi Chaker Hospital. Analysis of clinical spectrum, diagnosis tools, and radiological appearances. RESULTS: Twenty seven cases of CLM have been investigated: 8 congenital lobar emphysema, 8 congenital cystic adenomatoid malformation, 8 pulmonary sequestrations, 2 bronchogenic cysts, and 1 hybrid lesion. Five (18,5%) patients were diagnosed antenatally and 22 (81,4%) postnatally. Symptoms occurred at a mean age of 9 months: Respiratory distress (11 cases), wheezing (4 cases), and pneumonia (7 cases). Antenatal ultrasound features include echogenic masses within the chest (2cases), the presence of cysts (2cases), unilateral pleural effusion (1 case) and hydramnios (2cases). A computed tomography scan was performed in all patients with a radio-histological concordance of 96%.

Hemophagocytic Lymphohistiocytosis: A Rare Complication of an Ultrarare Lysosomal Storage Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory condition that may be triggered by infections, autoimmune and immunologic disorders, malignancies, and metabolic diseases. Early and accurate diagnosis of HLH and its underlying cause is of paramount importance for proper management and prognosis. We report the case of a Tunisian 21-month-old girl who initially presented clinical features of HLH related to a lysosomal acid lipase deficiency. The genetic sequence analysis of the LIPA gene revealed a never described homozygous mutation c.966G>C (p.Gln322His). The parents were heterozygous for this mutation. Enzyme replacement therapy was not provided for the patient. She received etoposide, corticosteroids, and cyclosporine for the HLH. She is waiting for hematopoietic stem cell transplantation. To the best of our knowledge, this is the second Tunisian case of secondary HLH complicating lysosomal acid lipase deficiency related to a new homozygous mutation: c.966G>C (p.Gln322His).

[Positivity of antineutrophil cytoplasmic antibodies in children: prevalence and etiologies]. / Positivité des anticorps anti-cytoplasme des polynucléaires neutrophiles chez l'enfant : prévalence et étiologies.

In adults, anti-neutrophil cytoplasmic antibodies (ANCA) are considered as serological markers of several diseases, especially vasculitis and glomerulonephritis. Since ANCA are rarely positive in children, few data about the clinical relevance of these auto-antibodies in pediatric population have been reported. Therefore, our study aims to describe the spectrum of disorders associated with positive ANCA in Tunisian children. This study had been carried out over a period of 12 years and a half. All patients under the age of 15 for whom ANCA screening was performed in our laboratory were included. Clinical data were collected retrospectively. Indirect immunofluorescence (IFI) technique for ANCA detection was performed using PNN smears fixed with ethanol, formalin and, if necessary, methanol. Positive results were tested using immunodot to characterize the antigenic targets (myeloperoxydase (MPO) and proteinase 3 (PR3)). Our results showed that 410/5,990 (6.8%) laboratory requests for ANCA screening were for children. Forty (9.7%) requests were positive (24 children). Clinical data were available for 19 patients only. Sex-ratio (F/M) was 1.25. The mean age was 9 years and a half (3-15 years). The most frequent IIF patterns were x-ANCA (n=12) and p-ANCA (n=7). In our patients, the most frequent conditions associated to ANCA were treatment with benzylthiouracil for hypothyroidism (n=6), inflammatory bowel disease (n=4) and hemolytic anemia (n=4). In conclusion, the positivity of ANCA in children seems to be a rare event. Associated conditions include clinical disorders specific to the pediatric population. Treatment with benzylthiouracil is an etiology to be taken into consideration.

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.

Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

Ataxia-telangiectasia in the south of Tunisia: A study of 11 cases.

BACKGROUND: Ataxia-telangiectasia (A-T) is a multisystem disorder characterized by progressive neurologic impairment, variable immunodeficiency, impaired organ maturation, X-ray hypersensitivity, oculocutaneous telangiectasia, and a predisposition to malignancy. AIM: We performed this study in order to describe clinical, immunological and molecular features of patients with AT followed in the south of Tunisia Methods: we performed a retrospective study (1996-2012) in the south of Tunisia about all cases of A-T in order to describe their clinical, immunological and molecular features. RESULTS: 11 cases of AT were found. The mean age at onset of symptoms was 20 months with extremes varying from 3 months to 4 years. The median time to diagnosis was 3.6 years (range: 0-12 years).The main clinical feature of cerebellar syndrome, ataxia, was present at diagnosis in 8 patients and occurred at mean ages of 2.8 years. Ocular telangiectasia occurred at a mean age of 3.9 years (extremes: 3 months and 7 years). Recurrent sino-pulmonary infections that affected 7 children occurred at the mean age of 4.3 years. The most common humoral immune abnormality was serum IgA deficiency. Lymphopenia was found in 7 cases and lack of CD4 T in 6 cases. Cytogenetic analyses showed chromosomal instability in all children and a translocation (7-14) in two patients. A molecular diagnosis established in 6 patients from 4 families showed 5 different mutations of ATM gene. After an average decline of 5 years and 6 months, 7 patients died of severe pulmonary infection. Among them, 3 were ATM mutated. CONCLUSION: Morbidity and mortality among patients with A- T are associated with ATM genotype.

[Primary immune thrombocytopenia in childhood: a regional study in the south of Tunisia]. / Thrombocytopénie immune primaire de L'Enfant: etude régionale dans le sud Tunisien.

BACKGROUND: the primary immune thrombocytopenia (ITP) in children has a favorable evolution in most of cases. aim: describe the epidemiological and therapeutic data and the outcome of primary immune thrombocytopenia in our patients and propose a treatment plan to standardize the management of this disease in our region. methods: We conducted a retrospective study of 140 cases of primary immune thrombocytopenia collected in department of pediatrics and hematology of Hedi Chaker hospital during a period of 15 years. Patients who had a platelet count ≤ 20 000 and / or mucosal or troublesome lifestyle hemorrhage were treated. results: The mean age was 6 years 7 months with extremes varying from 3 months to 15 years. The bleeding manifestations were dominated by cutaneous bleeding in the form of petechiae or bruise (100%). Epistaxis and gingivorragia were noted in 32,9% and 25,7% of the cases respectively. The most of patient were treated with corticosteroids (79%). Intravenous immunoglobulin was associated with corticosteroids in 7%. An acute ITP occurred in 94 cases (67%) and a chronic ITP in 30 cases (21%). CONCLUSION: In the recently diagnosed ITP, the response delay under association Intravenous immunoglobulin and corticoids is shorter than that of corticoids alone, but the high cost of Intravenous immunoglobulin associated with their immediate side effects compels us to recommend corticoids as a first line of treatment.

[Bacterial meningitis in children: epidemiological data and outcome]. / La méningites purulentes de l'enfant dans le sud Tunisien: aspects épidémiologiques et évolutifs.

BACKGROUND: The bacterial meningitis in children remains a worrisome affection both by its frequency and by its gravity. AIM: describe the epidemiological, clinical and evolutionary data of bacterial meningitis in children aged between 3 months and 15 years. METHODS: we conducted a retrospective study of all cases of bacterial meningitis collected in the department of pediatrics of Hedi Chaker hospital, during a period of 6 years (2006-2011). We analyzed the files retrospectively and we studied the epidemiological data and the outcome. RESULTS: Thirty cases of bacterial meningitis were recorded. The most frequent species were Streptococcus pneumoniae and Haemophilus influenzae followed by Neisseria meningitidis with respectively 43%, 40%, and 6% of cases. The yearly distribution of these bacteria showed an increase of the rate of the bacterial meningitis during the last 2 years. The average age of our patients was 1 year 6months (3 months-13 years). All the patients were vaccinated according to the Tunisian vaccination calendar; and none of them had pneumococcal vaccine or the Hib vaccine. The main clinical manifestations were fever (100 %), seizures (14 %) and vomiting (44 %). Bulging fontanel was noted in 15cas (55 %), somnolence in 11 cases (40 %) and axial hypotonia in 12 cases (44 %). In the outcome, the neurological sequelae were showed in eight patients (26%). CONCLUSION: In our study, H. influenzae and S. pneumoniae were the main microorganisms responsible for bacterial meningitis. We strongly recommend the introduction pneumococcal vaccine in our vaccination calendar.

[Cerebral imaging in epileptic children: study of 140 cases]. / Magerie cérébrale de l'épilepsie de lenfant. Etude de 140 observations.

BACKGROUND: Epilepsy is a chronic disease, often with an onset during childhood and characterized by spontaneous and recurrent seizures. It concerns 0.5-1% of children under 16 years of age. Being much more sensitive than computed tomography, magnetic resonance imaging is the technique of choice to identify an underlying cause. CT scan is used in emergency situations. AIM: To describe cerebral lesions in epilepetic children and to identify predicative factors of abnormal neuroimaging. METHODS: Authors present a retrospective descriptive study of Neuroimaging data of 140 epileptic children evaluated for a period from 2000-2007 in the paediatric departement of Sfax. RESULTS: The mean age at onset of seizures was 3 years. The sex ratio was 1.12. Psychomotor retardation was noted in 75 patients. The seizures were generalized in 75% of case. Neurological examination was abnormal in 73 cases (52%). The main indications for conducting a brain imaging were psychomotor retardation (65 cases) and focal onset seizures (25 cases). Anoxo-ischemic lesions were the most frequent cerebral anomalies followed by brain malformations. Predictors of pathological MRI were an age at onset of seizure <3 years, psychomotor retardation and abnormal neurological examination. CONCLUSION: The morphological imaging is recommended for recent seizures of the child with the exception of idiopathic epilepsies. MRI is the best imaging modality in exploration of epilepsy in this context.

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.