INTRODUCTION:Children with transfusion dependant diseases are confronted with multiple physical, psychosocial and cognitive obstacles, which touches significantly on their well-being and quality of life. AIM:to assess the quality of life of children with transfusion-dependent diseases using the PedsQL 4.0 scale. METHOD:This was a descriptive and a cross-sectional study conducted on children with chronic regular transfusion therapy in the paediatric department A of Hedi Chaker Hospital in Sfax, Tunisia between December 2024 and Mai 2025. We collected demographic informations about the children and their families and the clinical characteristics of the disease. The quality of life was assessed using the PedsQL 4.0 Generic score scales for children aged over 5 years old. RESULTS:Fifteen children requiring chronic transfusion therapy were included. Eleven families belonged to a low socio-economic class. The mean score of the children's quality of life was 58.3%. The quality-of-life dimension with the highest score was the social function with a mean score of 67% while the dimension with the lowest score was the physical function with a mean score of 50.6%. CONCLUSION:Transfusion dependant diseases have major negative impact on the daily lives of affected patients. Understanding the challenges faced by these children and their families is important to guide management decisions aimed not only at prolonging life, but also at improving their overall quality of life.

BACKGROUND AND AIM:Megaloblastic anemia (MA) is a rare pathology in childhood due, in the majority of cases, to a deficiency of folic acid and/or vitamin B12 (cobalamin). This study aims to determine the epidemiological, clinical, and paraclinical profiles of MA in children and to specify its etiologies, therapeutic modalities, and treatment responses. METHODS:This is a retrospective descriptive study of MA cases in children carried out in the General Pediatrics Department of the Hedi Chaker University Hospital of Sfax over a period of 42 years, from January 1979 to December 2021. We included all the patients under 16 years old with a myelogram showing megaloblastosis. The selected patients' demographic characteristics, physical signs, laboratory findings, and treatment responses were recorded. RESULTS:Twenty cases of MA were collected, including 11 boys and 9 girls. The incidence of MA in children was 0.014%. The median age at diagnosis was 3.37 years. The clinical presentation was anemic syndrome with pallor and asthenia in all the cases. Neurological manifestations were noted in 2 cases and digestive disorders in 10 cases. Seven infants had psychomotor delays. On admission, all our patients had anemia with an average value of 5.6 g/dl. It was macrocytic in 19 cases. The blood count also revealed leukopenia (7 cases), thrombocytopenia (10 cases), and pancytopenia (5 cases). The myelogram showed megaloblastosis in all the cases and sideroblasts in one. A brain MRI was performed on five patients, and it showed abnormalities in three cases. The etiological investigations revealed a vitamin B12 deficiency secondary to a maternal Biermer's disease (6 cases), malnutrition (3 cases), Imerslund's disease (3 cases), congenital deficiency in transcobalamin II (3 cases), Biermer's disease (1 case), giardiasis (1 case), folic acid deficiency secondary to a poor dietary intake (1 case), mitochondrial cytopathy with vitamin B12-Folic acid deficiency (1 case), and Pearson syndrome (1 case). Our treatment included symptomatic measures, replacement therapy, and etiological treatment. Favorable evolution was noted in 11 cases. Five patients had neurological sequelae, and one patient died. CONCLUSION:Our study highlights the rarity and heterogeneity of the etiological contexts of MA in children. Early diagnosis and therapeutic support can improve the long-term neurological prognosis.

Introduction Arteries in children. Untreated, approximately 25% of patients develop coronary complications, making KD the most common vasculitis in children under 5 years of age. While its incidence is highest in Japan, data from Tunisia remain limited. Early diagnosis and treatment with intravenous immunoglobulins (IVIG) significantly reduce the risk of coronary artery lesions (CAL). Method This study aimed to analyze the clinical and echocardiographic features of cardiovascular involvement in a cohort of Tunisian children with KD and identify risk factors associated with cardiac complications. Methods A retrospective, descriptive, and analytical study was conducted at Hédi Chaker University Hospital in Sfax, Tunisia, from January 2015 to December 2021. Children under 14 years diagnosed with complete or incomplete form of KD according to the American Heart Association (AHA) criteria were included. Data on clinical, biological, and echocardiographic features were collected. Statistical analysis was performed using IBM SPSS version 20, with multivariate logistic regression to identify risk factors for CAL. Results Among 32 patients (18 girls, 14 boys; mean age 3.6±2.6 years), 65.6% had incomplete KD. Cardiac involvement was observed in 78% of cases (n=25), including coronary artery dilation (n=23), hyperechogenicity of coronary arteries (n=15), and aneurysms (n=4). The left coronary artery was more frequently affected (n=19). Elevated C-reactive protein (CRP≥50mg/L; p=0.002) and leukocytosis (≥15,000/mm3; p=0.04) were independent predictors of CAL in multivariate analysis. All patients received IVIG (2g/kg) and acetylsalicylic acid, with favorable outcomes. Conclusion Incomplete form of KD was predominant in this Tunisian cohort, with a high prevalence of CAL. Elevated CRP and leukocytosis were significant risk factors for cardiac involvement. Early identification of these predictors may improve risk stratification and guide timely intervention to prevent coronary complications.

INTRODUCTION:congenital thrombopathies (CTs) are rare bleeding disorders resulting from platelet dysfunction which may also be associated with thrombocytopenia. To date, the prevalence of CT in Tunisia has not been established. AIM:The aim of this study was to describe the various types of CT and the associated hemorrhagic manifestations observed in a cohort from southern Tunisia. METHODS:We retrospectively collected clinical and laboratory data of patients with CT who were followed up over 43 years (1982 - 2024) in the pediatric and hematology departements of a university hospital center in southern Tunisia. The diagnosis of thrombopathy was established based on flow cytometry analysis and/or light transmission aggregometry and/or molecular analysis. RESULTS:We identified 60 patients (35 men and 25 women). The mean age at diagnosis was 61.7 months (1 month-70 years). Consanguinity was noted in 71.6% of cases (n=43). A family history of thrombopathy was reported in 51.6% of cases (n=31). The presenting symptoms at diagnosis were spontaneous or provoked bleeding (n=56) and easy bruising associated with thrombocytopenia within the first 48 hours of life (n=1). The etiologies of the thrombopathies were as follows : Glanzmann thrombasthenia (n=54), Bernard Soulier syndrome (n=5) and Wiskott Aldrich syndrome (n=1). CONCLUSION:Glanzmann thrombasthenia was the most prevalent thrombopathy in our cohort, likely attributed to the high rate of consanguinity in our region.

Background Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and the most common indication for cardiac transplantation in young adults. The clinical spectrum of DCM is heterogeneous, ranging from asymptomatic left ventricular dysfunction to advanced heart failure, arrhythmias, and sudden cardiac death. Methods Whole-exome sequencing (WES) was performed on germline DNA of the index case followed by segregation analysis of the identified variants on family ‘members by Sanger sequencing. Results We identified in the proband, a boy aged of 2-years, heterozygous germline nonsense variant in the TTN gene (c.95008C>T, p.Arg31670*), combined with other nonsense variant in the CTNNA3 gene (c.2023G>T, p.Glu675*). Segregation analysis revealed that both variants co-segregate with the disease phenotype within the family. This is the first report of the co-occurrence of pathogenic/likely pathogenic nonsense variants in TTN and CTNNA3 genes in DCM patients. Conclusions Our findings expand the mutational spectrum of DCM in North African populations and underscore the importance of genetic screening in familial cardiomyopathies.

Background Dihydrolipoamide dehydrogenase deficiency (DLDD) (OMIM# 246,900) is an extremely rare inherited metabolic disorder causing neurological and/or liver impairment. The clinical manifestations are mostly characterized by severe neurological impairment in early childhood, hepatic presentations and rarely by myopathic manifestations. Case presentations Here, we describe two patients presenting with recurrent episodes of vomiting and liver dysfunction. DLDD was confirmed via sanger sequencing by identification of the pathogenic variant c.685G > T (p.Gly229Cys) in DLD gene at a homozygous state. Conclusion To our knowledge, this is the first Tunisian report of DLDD. Phenotypic spectrum of this disease is very large. Biochemical markers that predict the impairment of the pathways affected by the deficiency of E3 subunit (gluconeogenesis, tricyclic cycle and catabolism of branched chain aminoacids) are variably present. Confirmation is based on genetic study of DLD gene.

BACKGROUND:Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. Congenital adrenal hyperplasia (CAH) is the most common cause of PAI in children. To date, numerous non-CAH causes have been identified through genetic analysis but they remain poorly characterized. OBJECTIVE:We aimed to describe the clinical presentation, etiology, genetic analysis, and long-term outcome of non-CAH PAI in children. METHODS:We retrospectively collected clinical and laboratory data from patients with non-CAH PAI who were followed up during a period of 33 years (1988-2020) at the pediatric department of a university hospital center in southern Tunisia. RESULTS:We identified 52 patients with non-CAH PAI (35 boys and 17 girls). The mean age at diagnosis was 4.8 years (0.05-18.7 years). Hyperpigmentation was the most frequent symptom at diagnosis (92.3%), followed by asthenia (84.6%), weight loss (57.7%), recurrent vomiting (53.8%), and dehydration (42.3%). The most prominent biochemical findings were hyponatremia (60.4%), hypoglycemia (35.4%), and hyperkalemia (16.6%). A total of 21patients (40.4%) presented with adrenal crisis at disease onset. The most common causes of non-CAH PAI were inherited genetic conditions and included Allgrove syndrome (n=15), X-linked adrenoleukodystrophy (n=10), autoimmune polyglandular syndrome (APS) type 2 (n=2), familial glucocorticoid deficiency type 1 (n=1), MCM4 mutation responsible for DNA repair defect (n=1), SF1 deficiency (n=1), APS type 1 (n=1), and autoimmune PAI (n=3). The cause of PAI remained unknown in 34.6% of cases. During follow-up, 24 patients (46.2%) presented with statural growth delay, and eight patients (15.4%) developed obesity. CONCLUSION:Allgrove syndrome was the most common etiology of non-CAH PAI in our study, followed by X-linked adrenoleukodystrophy. Today, advanced molecular analysis can be useful for diagnostic investigations, especially in patients with no specific diagnostic features.

Congenital sideroblastic anemia (CSA) is a rare genetic disorder caused by defects on heme biosynthesis and mitochondrial energy production. This disease is characterized by the presence of ring sideroblasts in the bone marrow caused by excessive iron accumulation in mitochondria of erythroblasts and by anemia of varying severity. In addition to its clinical variability, CSA is also characterized by genetic heterogeneity which required next-generation sequencing technologies to identify responsible gene. In the present study, whole-exome sequencing followed by Sanger sequencing were performed on a consanguineous family including two patients with congenital sideroblastic anemia. Mitochondrial DNA deletion and copy number were tested respectively by long PCR and QPCR. Subsequent bioinformatic investigations were performed using several programs. WES and Sanger sequencing results revealed a novel pathogenic variant c.579-580insT (p.N194X) in the PUS1 gene. Several bioinformatic tools supported that this variant was disease-causing. This variation leads to an incomplete catalytic site which will be probably non-functional and could disturb heme biosynthesis. In addition, no mtDNA deletion was detected in the two patients whereas mtDNA quantification revealed a decrease of mtDNA copy number in P2 and its increasing in P1. The increase in mtDNA copy number, which is most likely connected to a compensatory mechanism, may be the cause of the moderate phenotypic severity observed in P1 with the same p.N194X variant with P2. In conclusion, we identified a novel truncated pathogenic variant in PUS1 gene in two siblings of consanguineous family with intrafamilial phenotypic variability related to mtDNA copy number.

Introduction Pulmonary hypertension is a life-threatening condition in newborns. While common causes include meconium aspiration, sepsis, and congenital diaphragmatic hernia, rare etiologies such as cerebral vascular malformations must be considered, particularly when standard therapies fail. Vein of Galen malformation (VOGM) is a rare congenital vascular anomaly that can lead to high-output cardiac failure and pulmonary hypertension due to increased cerebral blood flow. This malformation is caused by a direct arteriovenous fistula between choroidal arteries and the embryonic median prosencephalic vein of Markowski (the precursor to the vein of Galen). There are two major anatomic subtypes: the choroidal type and the mural type. Mortality is especially high during the neonatal period. Without intervention, over 90% of these infants progress rapidly to multiple organ failure. Method Here, we report the case of a 2-day-old female newborn presenting with severe pulmonary hypertension refractory to medical management with high output heart failure, ultimately diagnosed with a choroidal-type VOGM. Results A full-term female newborn was delivered via cesarean section to a diabetic mother. She exhibited tachypnea and mild desaturation. Physical examination revealed prominent jugular venous pulsations, and hepatomegaly. Chest radiography showed significant cardiomegaly. Transthoracic echocardiography revealed a structurally normal heart with dilated right-sided cavities (Figure 1a), isosystematic pulmonary arterial hypertension, diastolic reversal flow in the proximal descending thoracic aorta (Figure 1b) and Continuous and prominent carotid flow with prominent superior vena cava flow. A cerebral vascular malformation was highly suspected. Subsequent computed tomography (CT) (Figure 1c) angiography and magnetic resonance imaging (MRI) confirmed a choiroidal -type vein of Galen malformation with significant arteriovenous shunting. Given the poor hemodynamic tolerance and the presence of isosystemic PH with a bicetre scale score of 12, emergent embolization was decided. A femoral arterial approach was performed, with embolization of three branches of the right and left posterolateral choroidal arteries, achieving occlusion of the shunts (Figure 1d). Conclusion PPHN in VOGM is a rare presentation and can be challenging to diagnose and to treat. This case underscore the importance of considering cerebral vascular anomalies in neonates with hig cardiac output heart failure and refractory pulmonary hypertension.

Periostitis ossificans, also known as Garré’s osteomyelitis, is a rare form of chronic osteomyelitis characterized by new bone formation with periosteal reaction. It most frequently affects the mandible, with common sources of infection being dental caries and periodontal lesions. This condition mainly affects younger patients. The therapeutic approach usually involves elimination of the infectious source, administration of antibiotics, and surgery if there is no response. This case is notable because no definitive source of infection was identified, which represents the main novelty of this report. The differential diagnosis with mandibular tumors or other inflammatory bone diseases made this case particularly challenging. We report the case of a 13-year-old boy from Sfax, Tunisia, who presented with chronic osteomyelitis with proliferative periostitis of the mandible. He had no identifiable source of infection. Imaging and histological findings confirmed Garré’s osteomyelitis. The patient was successfully treated with intravenous antibiotics. At 10-month follow-up, he remained asymptomatic with a symmetrical facial morphology. This case highlights the importance of considering Garré’s osteomyelitis in the differential diagnosis of mandibular swellings in adolescents, even in the absence of an evident infectious source. It also demonstrates the successful nonsurgical management of nonodontogenic Garré’s osteomyelitis.

Progressive familial intrahepatic cholestasis type 5 is a rare cause of neonatal cholestasis with low-to-normal levels of gamma-glutamyl transpeptidase. It is caused by mutations in the NR1H4 gene, which encodes farnesoid X receptor, an important transcription factor for bile formation. It also plays an essential role in biliary acid homeostasis. It is known to have a severe course with a rapid progression to end-stage liver failure. Very few cases have been reported worldwide. The authors report the case of a 2-month-old female infant presenting with prolonged jaundice due to progressive familial intrahepatic cholestasis type 5. The laboratory assessment showed a normal level of gamma-glutamyl transpeptidase and an elevated rate of serum bilirubin, transaminase activity, bile acids, and alpha-fetoprotein. Whole-exome sequencing identified a novel homozygous pathologic variant in the NR1H4 gene, described for the first time. At the age of 6 months, the patient died because of liver failure and disseminated intravascular coagulation. In conclusion, this is the first Tunisian case report of PFIC type 5; the diagnosis was made based on a molecular study. The off-label use of ursodeoxycholic acid was ineffective.

CONTEXT:Primary adrenal insufficiency (PAI), a rare and potentially life-threatening disorder, involves genetic factors in over 80% of pediatric cases. Congenital adrenal hyperplasia (CAH) is common, while the prevalence of other genetic factors varies between countries. OBJECTIVE:This study investigated the clinical and molecular genetic characteristics of a Tunisian PAI sub-cohort. Identifying causal variants is crucial for patient care, genetic counseling, follow-up and preventing complications. Determining variant prevalence will help in shaping a cost-effective molecular strategy in a country with limited resources. PATIENTS AND METHODS:Seventy-four patients from 65 families, with suspected congenital PAI, excluding CAH and autoimmune disease, were recruited. Clinical details were assessed by endocrinologists. Genetic analysis used a candidate gene approach (AAAS, ABCD1) and/or targeted enrichment with focused gene panels and next-generation sequencing (NGS). The pathogenicity of rare variants was assessed on in silico analysis. RESULTS:The study achieved a diagnostic yield of 86% (56/65 families), confirming 45 patients with Allgrove syndrome (Triple A) and identifying 12 boys with adrenoleukodystrophy. The recurrent Maghreb variant (c.1331+ 1G>A) was identified within the AAAS gene. NGS revealed additional defects, including AAAS and ABCD1 variants in atypical cases (n=3). Other etiologies included MC2R (n=1), NNT (n=1), STAR (n=2, 1 family), MCM4 (n=1) variants; 14% remained undiagnosed, some with variants of uncertain significance. CONCLUSION:This study of Tunisia's largest PAI cohort confirmed the efficacy of the candidate gene approach. NGS significantly increased diagnostic yield (11%) and identified candidate variants. Achieving molecular diagnosis in almost 90% of children has implications for patient management, genetic counseling, monitoring and the prevention of complications.

le rhumatisme articulaire aigu (RAA) est une maladie multi-systémique, au cours de laquelle l'atteinte cardiaque constitue toute la gravité de la maladie. L'objectif de notre étude était d'analyser l'atteinte cardiaque au cours du RAA et ses facteurs de risque. . Il s'agissait d'une étude rétrospective incluant tous les patients hospitalisés pour RAA, au service de pédiatrie du CHU Hédi Chaker de Sfax, durant une période de 12 ans (2010–2022). Le diagnostic de RAA a été retenu en se basant sur les critères de Jones modifiés par « l'American Heart Association » en 1992 puis révisés en 2015. Nous avons colligé 50 cas de RAA (31 garçons et 19 filles). Vingt-deux enfants (44 %) ont développé une cardite rhumatismale (CR). L'âge moyen au moment du diagnostic était de 9,6 ans [5–14 ans]. À l'examen cardiologique, nous avons noté un souffle cardiaque chez 14 patients (n = 14/22), un seul patient a présenté une insuffisance cardiaque et huit enfants ayant une CR étaient asymptomatiques (CR sub-clinique). L'échographie cardiaque a montré une atteinte valvulaire tous les cas de CR avec une péricardite associée dans un cas. La valve la plus touchée était la valve mitrale avec une insuffisance mitrale isolée dans 9 cas. Les lésions cardiaques ont été classées en cardite légère dans 15 cas, modérée dans 5 cas et sévère dans 2 cas. La durée médiane de suivi était de 3,3 ans ; dix-neuf enfants ont gardé des séquelles valvulaires. Les facteurs prédictifs de ma survenue d'une CR étaient : un âge supérieur à 8 ans, la présence d'un souffle cardiaque, l'allongement de l'espace PR à l'ECG, une CRP supérieure à 100 mg/l et une VS supérieure à 100 mm à la première heure. Les CR constituent encore un problème de santé publique en Tunisie. Il s'agit d'une pathologie grave avec une morbidité importante, d'où l'intérêt de renforcer les stratégies de prévention primaire et secondaire. 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. 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). 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. 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.

OBJECTIVE:the aim of this study is to report epidemiological data, clinical presentations and management of chronic immune thrombocytopenic purpura (ITP) in a single center in south of TUNISIA. METHODS:retrospective study collecting all cases of chronic ITP among children aged less than 14 years, in a department of pediatrics in south of Tunisia during a period of 13 years (from 1st January 2010 to 31 December 2022) Results: during the study period, 72 newly diagnosed ITP were recorded; 11 patients evolves chronic ITP (12 ,5%). They were 6 boys and 5 girls. Two patients were aged more than 10 years at the onset of the disease. Symptoms in the chronic stage were mucocutaneous bleeding. One patient developed post traumatic cerebral hemorragia. Three patients had severe form, and required second-line therapy. Two patients requested Eltrombopag with good response. One patient had spontaneous recovery after 3 years of follow up. CONCLUSION:Management of chronic ITP represents a real challenge for pediatrician. Currently, there are some recommendations and guidelines which can guide management strategy of severe forms of Chronic ITP.

Bannayan-Zonana syndrome (BRRS) is a rare genetic disorder characterized by macrocephaly, numerous soft tissue and visceral hamartomas, and lipomas. Because of the risk of fatal bleeding and visceral neoplasia in adulthood, recognizing this disease is critical. We reported a new pediatric case of BRRS in an 18-month-old female infant with lipomas, macrocephaly, and gastrointestinal hamartomatous polyps that prompted ileo-ileal intussusception and protein-losing enteropathy. Patients with BRRS require a comprehensive approach. Our case is unique in its sporadic occurrence and the presence of protein-losing enteropathy as a gastrointestinal polyposis manifestation. Pediatric patients with multiple lipomas, protein-losing enteropathy, and intestinal intussusception should be assessed for BRRS.

Miliary tuberculosis (TB) is a severe form of disseminated TB. In pediatrics, many cases are missed because the symptomatology of TB mimics common childhood diseases. We present the case of a 6-year-old girl with no remarkable history who had recurrent fever for 3 months. She was initially diagnosed with, and treated for, refractory multisystem inflammatory syndrome in children (MIS-C). When the study was extended to other differential diagnoses, thoraco-abdominopelvic computed tomography revealed miliary pulmonary nodules in addition to lymph nodes and spleen lesions. Magnetic resonance imaging of the brain revealed multiple tuberculomas. The tuberculin test results were positive. The course of the disease was favorable under quadruple therapy. (c) 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

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.