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.

Objectives: Glioblastoma (GB) is a heterogeneous group of tumors with poor patient's outcome. The epigenetic markers could influence patient's outcome and add more precision in sub-typing. Methods: The study aims to determine a correlation between the methylation status of 65 genes and the overall survival (OS) in 50 GB Tunisian patients using methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) technique. Results: OS was significantly longer for patients with tumors harboring unmethylated tumor suppressor genes ATM, BRCA1, BRCA2, TP53 and TP73 and the DNA repairing gene MSH6. Furthermore, simultaneous unmethylation of ATM, BRCA2, CD44 and VHL genes was associated with GB presenting normal EGFR status. This subgroup exhibits a better prognosis (OS=15 months, p=0.005). Our results also showed that, combined methylation of TP73, THBS1, GSTP1 and ESR1 genes in amplified EGFR GB subtype resulted in a poor prognosis group (OS=3 months, p=0.041). Simultaneous methylation of HLTF and SFRP5 genes was associated with wild-type IDH1 GB defining therefore a very poor prognosis group (OS=1 month, p=0.026). Besides, BRCA1 methylation in wild-type IDH1 group was significantly associated with poor prognosis (OS=6 months, p=0.002). Interestingly, RBM14 and PCCA genes were co-methylated in 80 % of prolonged survival cases (GB+). In absence of EGFR amplification and with unmethylation of BRCA1, BRCA2, ATM, VHL, CD44, HLTF and SFRP5 genes, GB+ tumors seemed to respond better to treatment, avoiding the relapse and conferring prolonged survival (>36 months). Conclusion: Combining genes methylation status of GB with EGFR and IDH1 profiles will refine subtyping, predict patient's outcomes and guide personalized therapy.

BACKGROUND: Mitochondrial diseases comprise a genetically and clinically heterogeneous group of disorders primarily resulting from defects in oxidative phosphorylation, leading to impaired ATP synthesis and cellular energy deficiency. The functional competence of mitochondria critically depends on the ultrastructural integrity of the inner mitochondrial membrane, notably the cristae, which serve as the platform for respiratory chain complexes. The mitochondrial contact site and cristae organizing system complex (MICOS) is essential for maintaining cristae junction architecture and inner membrane morphology. Disruption of this complex, especially mutations affecting the MIC13 subunit, compromises cristae junction integrity, leading to severe multisystem mitochondrial cytopathies with prominent neurological and hepatic manifestations. METHODS AND RESULTS: We report here a consanguineous family with a patient presenting with cholestatic hepatopathy, profound developmental delay, optic atrophy, sensorineural hearing loss, microcephaly, and cerebellar atrophy. Whole-exome sequencing performed in the patient identified a homozygous pathogenic novel c.209dupT (p. A73Rfs*32) variant in the MICOS13 gene inherited from his heterozygous parents. The variant introduces a premature termination codon, leading to a truncated protein that lacks the second RDSWN motif, which is critical for MIC13 function. Protein modelling and molecular dynamics simulation support the hypothesis that the mutation induces structural destabilization, impairing protein folding and function, which may contribute to mitochondrial dysfunction. Additionally, analysis of mitochondrial DNA copy number revealed a mitochondrial depletion in the patient. CONCLUSIONS: This case expands the clinical and molecular spectrum of MICOS13 deficiency, causing mitochondrial hepatoencephalopathy.

PFIC4 is a chronic liver disease which cannot be diagnosed based on clinical and biochemical findings with an unpredictable evolution. Here, we reported three consanguineous families with 9 children suffering from intrahepatic cholestasis with low GGT-activity. Three probands were chosen to undergo genetic testing. In silico analyses were conducted to assess the functional impact of the identified variant, along with variants occurring at highly conserved positions within the protein. Additionally, close clinical monitoring was carried. Targeted-NGS sequencing ruled out the diagnosis of PFIC1 and PFIC2. Subsequently, WES allowed the establishment of PFIC4 diagnosis for the three families through the identification of a homozygous TJP2 variant p. Gly532Arg classified as likely pathogenic with a structural damage predicted based on biomolecular modeling and simulation analysis. In-depth in silico analysis of 90 nsSNPs occurring in highly conserved residues in PDZ domains showed 14 ones seems to be relevant in the clinical practice. Clinically, a pronounced phenotypic variability is noted. In conclusion, our study described a homozygous missense PFIC4-related variant with a highlight on the pathogenic power of such types of variants. The clinical evaluation provided information about the importance of close monitoring to prevent liver failure and clarified the unexpected course of PFIC4.

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.

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.

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.

Background: Deep vein thrombosis (DVT) of the lower limbs in the elderly is a major health problem, despite improved prophylaxis and diagnostic advances. It must be managed rapidly and effectively. The aim was to determine the main features and risk factors (RFs) of DVT in elderly patients admitted to internal medicine. Methods: This was a retrospective, descriptive study carried out in the internal medicine department of Hedi Chaker Hospital in Sfax, over a period of 18 years. Records of patients hospitalized in the department during this period were reviewed. Results: There were 102 cases, divided into 64 men (62.8%) and 38 women (37.2%), with an average age of 75.2 years. DVTs in the veins of the lower limbs were most often proximal (75%). In addition to advanced age, considered an independent RF for DVT, at least one RF for VTE was found in 54.6% of cases. Bed rest was the most frequent RF, noted in 44 cases (43.7%). A thrombogenic pathology predisposing to thrombosis was retained in 25 patients, i.e., 24.5% of cases. These were SAPL (11 cases), neoplasia (12 cases), Behçet’s disease (1 case), and hyper-homocysteinemia (2 cases). Conclusion: DVT in the elderly, a frequent pathology, poses above all a problem of etiological diagnosis. Identifying the RFs for recurrence in this population is important, as it enables appropriate prescription of anticoagulants. Such treatment is not without risk in elderly patients who are frequently polythematic, with a high excess risk of bleeding.

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.

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.

Après un premier épisode de thrombose veineuse profonde non provoquée, le risque de récidive persiste pendant de nombreuses années.Un traitement anticoagulant à long terme prévient la récidive des thromboses veineuses mais est associé à un risque hémorragique majeur.Comme les plaquettes jouent également un rôle dans l'initiation et la formation du thrombus dans la maladie veineuse thrombo-embolique (MVTE), les anti-agrégants plaquettaires peuvent également jouer un rôle dans le traitement et la prévention de cette maladie.Cette mise au point résume les données de la littérature sur l'effet de l'aspirine dans la prévention des récidives de la thrombose veineuse profonde.

Purposes: Retinal vein occlusion (RVO) is a major cause of vision loss. Its pathogenesis is still not completely understood. Our aim was to describe patients with RVO, to precise risk factors responsible to retinal vasculopathy in our population and to assess the prevalence of thrombophilia disorders patients with RVO, compared to population-based group of age- and sex-matched controls. Patients & methods: Our study was retrospective conducted from 1 January 2013, until 30 June 2019, including 57 patients with RVO compared to 105 controls patient’s age- and sex-matched free of any visual disorders. Among 57 RVO cases, 26 were men and 31 were women. Results: The mean age was 45.0±14.7 years. Among systemic and ocular risk factors for RVO we found hypertension in 12 patients (31.6%), dyslipidemia in four patients (10.5%), diabetes in four patients (10.5%), and smoking in six patients (16.2%). Three patients (9.7%) had glaucoma and two patients (6.5%) had diabetic retinopathy. Ophthalmology examination found unilateral RVO in 52 patients (91.0%) and bilateral RVO in five patients (11.1%). Retinal angiography showed ischemic signs in seven patients (18.4%). Non-ischemic RVO was retained in 31 cases (81.6%). Macular edema was present in 12 patients (38.7%). Six cases (19.4%) developed neovascular glaucoma and two cases (6.5%) presented reversible blindness. Measures of thrombophilia practiced in 57 patients revealed 13 abnormalities (22.8%): Isolated thrombophilia disorder in 11 patients (71.4%) and combined prothrombotic disorder in two others. Conclusions: Among systemic and ocular risk factors for RVO, we found hypertension in 12 patients (31.6%). Thrombophilia disorders were also common.

Abstract Introduction: Castleman’s disease (CD), known as angiofollicular lymph node hyperplasia, is an uncommon condition. The two most common histological subtypes are hyaline vascular and plasma cell. We performed a retrospective analysis to define the clinic-pathological features and survival of CD, which is quite rare focusing on the particularities of our series with a review of the recent literature. Methods: This is a retrospective study conducted in the department of internal medicine of Hedi Chaker hospital in Sfax, Tunisia over 25 years. The disease was histologically confirmed in all patients. For each file, we collected a set of data by filling in a pre-designed form. Results: 18 patients were included. There were 8 men and 10 women with a mean age of 42.8 years. CD was monocentric in 5 cases (28%) and multicentric in 13 cases (72%). Clinically, peripheral adenopathy was present in 77.7% of patients and deep adenopathy in 72.2%. Systemic signs were found in 13 patients, including general condition (4.4%), fever (16.6%), serositis (27.7%), and skin involvement (33.3%). A biological inflammatory syndrome accompanied the clinical picture in 66% of patients. Abnormalities in the blood count were found in 12 cases (66%), with anemia in 11 cases, thrombocytosis in 3 cases, and hypereosinophilia in 3 cases. Cutaneous Kaposi’s sarcoma was associated with Castleman’s disease in 2 cases, Hodgkin’s lymphoma, angioimmunoblastic T-cell lymphoma, and lymph node T-cell lymphoma were found in 1 case respectively. 3 of the patients had associated connective tissue diseases such as Sjögren’s syndrome in 2 cases and rheumatoid arthritis in 1 case. HHV8 serology was positive in 1 case with a multicentric plasma cell form. Histologically, the plasma cell form represented 50% of cases, hyaline-vascular (39% of cases), and mixed (11% of cases). Therapeutically, high-dose corticosteroid therapy was initiated in 13 cases. As a second-line treatment, MOPP chemotherapy was used in 1 case due to transformation into Hodgkin’s lymphoma, and biotherapy (rituximab) was used in 2 cases in the multicentric form. Surgical removal of superficial adenopathy was performed in 2 patients with monocentric CD. Conclusion : Castleman’s disease (CD) is a non-malignant lymphoproliferation of localized or multicentric form with a wide and heterogeneous clinical spectrum. Diagnosis can be difficult due to the lack of clinical and radiological specificity. Management depends on the clinical form involving surgical and/or medical management.

After a first episode of unprovoked vein thrombosis, the risk of recurrence persists for many years. Long term of anticoagulant therapy prevents the recurrence of vein thrombosis but is associated with a major risk of bleeding. As platelets play a role in the initiation and propagation of venous thromboembolism as well, antiplatelet agents, may play a role in the treatment and prevention of this disease. This review summarizes available evidence on effect of aspirin in the prevention of recurrent deep vein thrombosis.

Le liposarcome, une tumeur maligne rare des tissus mous, est une forme particulière de sarcome qui se développe à partir du tissu graisseux. Il s'observe plus fréquemment chez l'homme et siège souvent sur les extrémités inférieures. Nous présentons le cas d'un patient âgé de 71 ans qui a consulté suite à l'apparition progressive d'une masse des tissus mous de la cuisse droite depuis 7 mois. L'examen clinique objectivait une masse ferme, légèrement douloureuse de la face interne de la cuisse droite faisant 10 × 15 cm non adhérente aux plans osseux sous-jacents. L'imagerie par résonance magnétique (IRM) de la cuisse montrait une masse graisseuse intramusculaire, bien limitée de 96 × 80 mm en axial et 180 mm en hauteur en hypersignal T1 et T2 avec chute du signal sur les séquences avec suppression de la graisse et annulation du signal sur la séquence STIR. Elle est traversée par des septa rehaussés et des structures vasculaires. Cet aspect IRM évoquait en premier lieu un liposarcome bien différencié de la cuisse droite. Cette hypothèse diagnostique était confirmée par l'examen anatomopathologique et immunohistochimique d'une biopsie de la tumeur. Le traitement consistait en une exérèse chirurgicale de la tumeur suivie de séances de radiothérapie. Liposarcoma, a rare malignant soft tissue tumour, is a particular form of sarcoma that develops from fatty tissue. It is most commonly seen in men and often occurs on the lower extremities. We present the case of a 71 year old patient who presented with a progressive soft tissue mass on the right thigh for 7 months. Clinical examination revealed a firm, slightly painful mass on the inner side of the right thigh measuring 10 × 15 cm not adherent to the underlying bony planes. Magnetic resonance imaging (MRI) of the thigh showed a well-limited intramuscular fatty mass measuring 96 × 80 mm axially and 180 mm in height with T1 and T2 hyper signal with a drop in signal on the sequences with suppression of the fat and cancellation of the signal on the STIR sequence. It is crossed by enhanced septa and vascular structures. This MRI appearance initially suggested a well-differentiated liposarcoma of the right thigh. This diagnostic hypothesis was confirmed by anatompathological and immunohistochemical examination of a biopsy of the tumour. Treatment consisted of surgical removal of the tumour followed by radiotherapy.

Advancements in Case Studies Severe Tophaceous Gout Imen Chabchoub*, Raida Ben Salah, Olfa Frikha, Faten Frikha, Sameh Marzouk and Zouhir Bahloul Department of internal medicine, Hedi Chaker Hospital, Sfax, Tunisia *Corresponding author: Imen Chabchoub, Department of internal medicine, Hedi Chaker Hospital, Sfax, Tunisia Submission:March 13, 2023;Published: March 30, 2023 DOI: 10.31031/AICS.2023.03.000574 ISSN 2639-0531Volume3 Issue5