Background Mastocytosis is a rare disorder characterized by abnormal proliferation and accumulation of mast cells. In children, it is most often limited to the skin. Diffuse cutaneous mastocytosis is the rarest form and typically presents during infancy, frequently with extensive bullous lesions. Due to its rarity and clinical resemblance to other bullous dermatoses, early diagnosis remains challenging. Case presentation We report the case of a 9-month-old female infant admitted for an extensive pruritic bullous and ecchymotic eruption involving the thorax, limbs, and scalp. Physical examination revealed thickened infiltrated skin and a positive Darier’s sign, while mucous membranes were spared. Routine laboratory investigations were normal. Skin biopsy showed a dense subepidermal dermal infiltrate composed predominantly of mast cells arranged in confluent sheets. Immunohistochemical staining demonstrated strong and diffuse CD117 positivity. Serum tryptase levels were elevated, supporting the diagnosis of diffuse cutaneous mastocytosis. The patient was treated with topical corticosteroids, sterile dressings, and oral antihistamines, with complete resolution of skin lesions and no systemic complications. Conclusion Diffuse cutaneous mastocytosis should be considered in infants presenting with bullous skin lesions. Histological and immunohistochemical confirmation is essential for diagnosis. Although prognosis is generally favorable, careful follow-up is required due to the risk of severe mediator-related manifestations. Clinical trial number: not applicable

BACKGROUND:Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic heart disease with a wide range of clinical manifestations, from asymptomatic cases to heart failure and sudden cardiac death. OBJECTIVES:To identify the disease-causing variants in patients with severe HCM by carrying on clinical examination and genetic analysis through 2 generations in a single family. PATIENTS AND METHODS:Family 'members underwent comprehensive cardiovascular examinations. Whole-exome sequencing was carried on the proband, a girl of five-years old followed by co-segregation and in silico analyses. RESULTS:The proband harboured a homozygous variant, NM_022915.5: c.198_205delinsTA; p.(Trp66_His69 delinsCysAsn), in the MRPL44 gene, leading to a shorter protein. This variant is novel, being absent in ClinVar and Human Gene Mutation Database (HGMD) and classified as VUS according to American College of Medical Genetics and Genomics (ACMG) criteria. Co-segregation analyses revealed that the proband's parents and her sister were heterozygous carriers, her other sister was wild-type, and her affected brother was homozygous for the mutation. In silico analysis showed significant structural differences in the mutated mL44 protein, disrupting its interaction with ribosomal complex components and impairing translation and protein synthesis. CONCLUSIONS:This study reports a novel MRPL44 variant associated with HCM in a Tunisian family. This finding expands current knowledge of genetic variations linked to mitochondrial cardiomyopathy and highlights the importance of genetic testing for diagnosis and management of cardiomyopathy.

Wilson's disease is an autosomal recessive disorder related to genetic defects in ATP7B gene and characterized by a hepatic and/or neurological impairment. This disease is often misdiagnosed on due to its phenotypic heterogeneity, supporting the importance of the genetic testing. In our study, we reported two brothers presenting with a chronic hepatopathy, classified as intrahepatic cholestasis with unknown etiology based on clinical explorations. A molecular screening through Whole-exome-sequencing was conducted, followed by sanger sequencing and co-segregation analysis in the family's members. Generated data were the subject of in silico analysis. Results revealed two pathogenic heterozygous variants in ATP7B gene (p.Met665Ile/ p.Gly869Arg) in compound heterozygous state in the analyzed proband and his brother. Predictive data supported their effect on the stability at the RNA and protein levels. In line of these data, additional clinical explorations were ensured and the Leipzig score was assessed to establish the WD diagnosis. Moreover, we identified two additional heterozygous variants shared by both siblings in CFTR (p.Thr351Ser) and PEX26 (p.Leu153Val), which may act as phenotype modifiers. Notably, both patients exhibited exocrine pancreatic insufficiency, raising the possibility of a contributory role for the CFTR variant in this atypical presentation. In conclusion, our study reveals a complex genetic background involving ATP7B, CFTR, and PEX26. While the ATP7B variants are responsible for WD, the additional variants may influence the age of onset and severity of the clinical phenotype. These findings underscore the value of high-throughput sequencing technologies in uncovering the molecular basis and phenotypic complexity of inherited diseases.

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.

Aim.- We conducted this study to assess the features of the IgE-mediated food allergies in children from Sfax hospital in South Tunisia and to study molecular component profiles for the main allergens. Patients and methods. - A review of laboratory records from children seen in the hospital-based Pediatrics Department between January 2016 and June 2020 was performed. We focused on patients with positive food-specific IgE, especially those with food allergy. Diagnosis of food allergy was established by pediatricians based on description of convincing symptoms from anamnesis occuring within minutes of food comsumption. The precise molecular targets of the circulating specific IgE were identified using components resolved diagnosis (CRD) in a well-characterized group of patients. Results. - We included 118 patients with food allergy (51% of all food-sensitized children). The mean age was 2.7 years [1 month-14 years] with a sex-ratio of m/f = 2,37. Most of patients had mild symptoms without life-threatening events. Main food allergens associated with food allergy in our patients were: cow's milk, egg white and peanuts. Cow's milk allergy was the most frequent (54%) in early childhood (mean age: 2,3 years [1 month-11 years]), and 85% of patients were polysensitized to cow's milk components. Sensitization to casein was associated with anaphylaxis and/or the persistence of allergy. Egg white allergy was found in 21% of patients (mean age: 3,9 years [4 months-12 years]). Ovalbumin, ovomucoid, and ovotransferrin were the most frequent components. Sensitization to ovomucoid was associated with severity and intolerance to cooked eggs. Allergy to peanuts was less common (8%) with main sensitization to the lipid transfer protein Arah9. Conclusion. - Specific IgE testing is useful in the context of food allergy and contributes to the diagnosis and management of patients. Disparities can be observed depending on the region/country. CRD is useful for diagnostic precision of food allergy. (c) 2023 Societe francaise d'allergologie. Published by Elsevier Masson SAS. All rights reserved.

Lyme neuroborreliosis (LNB) is a rare infectious disease, caused by Borrelia burgdorferi spirochetes and responsible for a variety of neurological manifestations. The most common manifestations of LNB in children are cranial nerve involvement, especially facial nerve palsy often accompanied by lymphocytic meningitis. In this article, we present a case of a 4-year-old boy presented to our emergency department with abdominal pain evolving for a week and symmetrical ascending progression of weakness responsible for severe respiratory failure. Diagnosis of Guillain-Barré syndrome (GBS) was initially suspected. Although our patient had received 2 courses (each of 5 days) of Intravenous immunoglobulin (IVG) treatment, no clinical improvement was observed. The diagnosis of LNB was confirmed by detection of both IgG and IgM specific antibodies in serum. The patient's muscle weakness got better after a 2- week course of Ceftriaxone but respiratory muscle failure didn't improve with two extubation failures. Consequently, we decided to conduct plasmapheresis procedures. We managed to extubate the child and discharge him after a good recovery of his symptoms. Pediatricians must consider LNB disease in the differential diagnosis of GBS, especially when the patient didn't recover after IVG treatment. This case shows that plasmapheresis could be effective for pediatric neuroborreliosis cases with severe neurological disorders.

Les anticorps anti-cytoplasme des neutrophiles (ANCA), marqueurs classiques des vascularites systémiques primaires des petits vaisseaux, ont 2 principales cibles antigéniques : la protéinase 3 (PR3) et la myéloperoxydase (MPO). La double positivité pour la PR3 et la MPO est inahbituelle en pratique courante. Sa relevance clinique n’est pas bien étudiée dans la littérature. Nous nous sommes proposés d’étudier la prévalence de la double positivité des ANCA à la MPO et à la PR3 et d’évaluer sa relevance clinique. Nous avons mené une étude rétrospective dans notre laboratoire d’Immunologie sur une période de 15 ans (2009–2023). Parmi tous les résultats ANCA positifs, nous avons inclus des patients positifs à la fois pour la MPO et la PR3 dans le même prélèvement. La recherche des ANCA a été effectuée par technique d’immunofluorescence indirecte (IIF) sur des polynucléaires neutrophiles fixés par un alcool (éthanol et formol) (Euroimmun®, Allemagne). La spécificité des ANCA a été déterminée par un test immuno-enzymatique (Euroline®, Allemagne) qui fournit des résultats semi-quantitatifs (+ : faiblement positif ; ++ : positif ; +++ : fortement positif). Parmi les 7906 demandes de recherche des ANCA reçues, 553 (7 %) étaient positives par IIF avec les aspects suivants : périnucléaire (pANCA) : n = 239 (3 %), pANCA atypique : n = 181 (2,3 %), et cytoplasmique (cANCA) : n = 133 (1,7 %). Les cANCA étaient principalement dirigés contre la PR3 (76 %) alors que les pANCA étaient dirigés contre la MPO (70 %) ou la PR3 (20 %). Six patients avaient des ANCA avec une double positivité concomitante anti-PR3 et MPO, soit 0,9 % de l’ensemble des patients ANCA positifs. Les données cliniques étaient disponibles que pour 4 patients (sex-ratio F/M : 1). Trois d’entre eux étaient des adultes (âge médian : 32 ans [25–33]). Deux patients étaient atteints de recto colite hémorragique (RCH) avec extension au côlon gauche. Aucun de ces deux patients n’a développé de complications ou de manifestations extra intestinales associées. L’aspect des ANCA était périnucléaire (pANCA). Les niveaux de positivité des ANCA pour la PR3 et la MPO étaient respectivement de (+)/(+) et de (+++)/(++). La 3ème patiente était une femme aux antécédents de méningite lymphocytaire et de COVID-19 suivie pour hypertension intracrânienne idiopathique. L’aspect des ANCA était cytoplasmique (cANCA). Le niveau de positivité pour la PR3 et la MPO était de (++)/(++) respectivement. Le dernier patient était un enfant de 4 ans atteint d’une colite indéterminée associée à une cholangite sclérosante primaire et à une hépatite auto-immune. L’aspect des ANCA était cytoplasmique (cANCA). Le niveau de positivite des ANCA était de (++) pour la PR3 et (+++) pour la MPO. Il est intéressant de noter qu’aucun de nos patients n’a présenté de signes de vascularite au bout d’un suivi moyen de 7 ans [1–12]. La double positivité concomitante des ANCA pour la MPO et la PR3 est rare dans la littérature ce qui est concordant avec nos résultats. Les vascularites associées aux ANCA et les infections chroniques sont les principales pathologies rapportées chez les patients présentant une double positivité concomitante pour la PR3 et la MPO. En dehors de contexte de vascularite, cette double positivité ne semble pas être associée à des particularités cliniques ou évolutives. Nos résultats montrent que les ANCA anti MPO et PR3 ne sont pas mutuellement exclusifs. Cette double positivité est rare, inhabituelle et peu spécifique puisqu’elle peut survenir dans de diverses situations cliniques autres que les vascularites.

IntroductionAlpha-Ketoglutarate dehydrogenase (2-KGD) deficiency, a rare disorder of the Krebs cycle, was described for the first time as a progressive neurodegenerative disease with 2-ketoglutaric aciduria in two siblings of a Tunisian consanguineous family by Kohlschutter and colleagues (1982) [1]. Alpha-Ketoglutarate dehydrogenase is a multienzyme complex that catalyzes the oxidative decarboxylation of a-ketoglutarate to succinyl-coenzyme A in the tricarboxylic acid cycle. It is made up of three components:E1 a-ketoglutarate lipoamide oxidoreductase.E2 dihydrolipoamide succinyltransferase transfers the carboxyl group to the coenzyme A moiety.E3 dihydrolipoamide dehydrogenase transfers reducing oxygen from E2 to a flavoprotein and finally to nicotinamide-adenine dinucleotide.Onset and clinical presentation of the reported cases of the (2-KGD) deficiency are heterogeneous, with mostly severe neurological impairment, including muscular hypotonia, developmental delay, extrapyramidal symptoms, ataxia, increased extensor tonus, and seizures. The age of onset varied between the neonatal period and 16 months. The oldest child reported died at the age of 10 years [1, 2, and 3].