S. Kmiha

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.

Factor XIII deficiency in south of Tunisia

&NA; Factor XIII deficiency is a rare autosomal recessive disorder of hemostasis characterized by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. The aim of the study is to describe the clinical features and the outcome of the patients and to determine molecular characteristics. A retrospective study, was conducted on seven patients with factor XIII deficiency in the department of hematology and pediatrics, Hedi Chaker Hospital, Sfax, Tunisia during the period of 14 years (2001–2014). The activity of factor XIII in plasma of the patients was less than 1%. Seven patients from five unrelated families were recorded (four men and three women). Median age at diagnosis was 3.5 years. All patients had consanguineous parents. Six patients presented umbilical bleeding and only three patients had intracranial bleeding. Other bleeding features were seen, including skin and mucosal bleeding, muscular hematoma, and splenic rupture. Recurrent abortions were observed in one patient. The standard screening tests were normal. Genetic analysis identified two mutations interesting the subunit A of factor XIII. All patients received transfusion of fresh frozen plasma monthly. One patient was died because of intracranial hemorrhage. Factor XIII deficiency is a rare bleeding disorder which frequently increases in areas with high consanguinity. In our study, we identified a founder mutation. The prognosis of the disorder is related to hemorrhagic complications especially to life-threatening intracranial bleeding. Prophylaxis consists of factor XIII concentrate or recombinant factor XIII. If these are unavailable, fresh frozen plasma may be used.

Transient neonatal diabetes mellitus and activating mutation in the KCNJ11 gene in two siblings

Transient neonatal diabetes mellitus is a rare disease usually associated with chromosome 6 abnormalities. Mutations of the genes encoding the potassium channel are rarely associated with these transitional forms. Herein, we report the clinical features of two siblings with a heterozygous mutation C679 G>A in the KCNJ11 gene.

SFP P-074 – Polyradiculonévrite aiguë primitive de l’enfant à propos de 20 cas

Objectifs Etudier les caracteristiques epidemiologiques, cliniques, electromyographiques, evolutives et therapeutiques du syndrome de Guillain-Barre (SGB). Patients et Methodes Etude retrospective, descriptive a propos de tous les cas de SGB colliges au service de pediatrie de CHU Hedi Chaker de Sfax durant une periode de 12 ans (2002–2013). Resultats L’âge moyen des malades etait de 4 ans 6 mois avec un sexe ratio de 1,2. Des manifestations prodromiques infectieuses ont ete observees dans 15 cas. Le deficit musculaire ainsi que l’areflexie osteotendineuse ont ete retrouves dans tous les cas. Une dissociation albuminocytologique etait notee dans 16 cas. Les manifestations electromyographiques etaient : une atteinte axonale dans 3 cas, axonomyelinique dans 5 cas et myelinique dans 12 cas. Le traitement specifique a base d’immunoglobulines polyvalentes intraveineuses a ete prescrit chez 15 malades. Une recuperation avec guerison totale etait observee chez 19 patients. Un malade est decede suite a une atteinte respiratoire. Conclusion L’evolution du syndrome de Guillain Barre le plus souvent favorable. La complication la plus redoutable est l’insuffisance respiratoire aigue.

SFP PC-34 - La maladie de pompe : à propos de 7 cas

Objectif Preciser les caracteristiques epidemiologiques, cliniques, biologiques, electro-physiologiques et radiologiques de nos patients et les comparer aux donnees de la litterature Patients Et Methodes Etude retrospective de 7 cas de la maladie de pompe colliges sur une periode de 6 ans allant du 1er janvier 2008 au 31 decembre 2013 Resultats Il s’agissait de 7 cas de forme infantile classique dont 5 garcons et 2 filles d’âge moyen de 3 mois. La principale circonstance de decouverte etait la dyspnee (6 cas). Une hepatomegalie et une hypotonie generalisee ont ete notees dans tous les cas. L’ECG a montre des signes d’hypertrophie ventriculaire gauche et des troubles de la repolarisation dans tous les cas. L’echocardiographie a montre une cardiomyopathie hypertrophique dans tous les cas. Le dosage de l’activite enzymatique realise dans 5 cas a montre une activite enzymatique nulle. L’etude genetique realisee dans 4 cas a montre une mutation du gene AAG a l’etat homozygote dans tous les cas. Le deces dans un tableau de defaillance cardio-respiratoire a ete note dans tous les cas a un âge moyen de 4 mois Conclusion Affection rare dont la frequence est probablement sous estimee dans notre pays ou le taux de consanguinite est eleve

SFP P-154 - La maladie de Rendu Osler à révélation prècoce : à propos d’une observation

But rappeler les aspects cliniques, therapeutiques et evolutifs de la maladie de Rendu Osler (MRO) a travers une forme severe et precoce de MRO. Observation S, âgee de 7 ans 8 mois, etait adressee pour exploration d’un retard de croissance avec hippocratisme digital. A l’examen clinique, elle avait un retard de croissance a -3DS, une cyanose des levres, une saturation en oxygene en l’air ambiant a 56% et un hippocratisme digital. L’echographie cardiaque etait sans anomalies. Le scanner thoracique ne montrait pas de syndrome interstitiel ni images de dilatation de bronches. L’angio-scanner thoracique mettait en evidence de multiples fistules arterio-veineuses (FAV) dont le diametre de l’artere nourriciere ne depassait pas 2mm. L’angio-scanner cerebral montrait 5 FAV et l’echographie doppler hepatique revelait 2 FAV. Un angio-scanner thoracique realise chez la mere montrait des FAV. L’etude genetique ne mettait pas en evidence de mutations au niveau des genes Endoglin et ACR1. Une abstention therapeutique etait decidee vu que les FAV pulmonaires etaient inaccessibles a une embolisation. Conclusion La MRO est une dysplasie vasculaire multisystemique, rare chez l’enfant. Le traitement des MAV pulmonaires repose sur l’embolisation par voie endo-vasculaire.

659 Hypoparathyroidism and Pseudo-Hypoparathyroidim: About 9 Cases

Introduction Hypoparathyroidism(HP) is an uncommon disorder of calcium metabolism characterized by hypocalcemia and hyperphosphatemia due to impaired parathyroid hormone (PTH) secretion. The pseudo-hypoparathyroidism(PHP) is characterized by a high level of PTH due to peripheral PTH resistance. Objective Describe clinical, biochemical, radiological profile, treatment and outcome in 9 patients with HP and PHP seen over a period of 24 years. Methods This study was performed in the pediatric department of Sfax during 24 years (from January 1988 to April 2012). The diagnosis of HP and PHP was based on demonstration of hypocalcemia, hyperphosphatemia with low or elevated PTH, respectively. Results During the period of study, 9 children having HP or PHP were admitted. There were 5 girls and 4 boys. The mean age at presentation was 44 months (15 days– 10 years). The most common presenting manifestation was seizures (8cases) followed by carpo-pedal spasm in one case. The mean serum calcium and inorganic phosphate concentrations were 1, 51 mmol/l and 3 mmol/l, respectively. Hypoparathyroidism’s etiologies were: autoimmune polyendocrine syndrome (2cases), idiopathic hypoparathyroidism (3cases), kearns sayer syndrome (1cas). PHP was diagnosed in 3 cases; among them, 2 children had Fahr syndrome. All patients were treated with oral calcium, active vitamin D. 2 patients died; the cause of death was not related to their HP. Conclusion HP is a rare endocrinopathy in childhood. The etiological diagnosis strategy needs many investigations especially genetic analysis.

641 Clinical and Epidemiologic Characteristics of Type 1 Diabetes in Children in a Pediatric Unit from Sfax (Tunisia)

Introduction During the last few decades, an increase in the incidence of type 1 diabetes (DT1) in children was reported in most parts of the word. Aims Study the epidemiologic and clinical particularity of (DT1) in our patients. Patients and methods From 2000 to 2011, children under 15 years with newly diagnosed type 1 diabetes mellitus and drown from department of pediatrics in Sfax were ascertained retrospectively. Cases of neonatal diabetes were excluded. Patients were devised on 3 groups: group 1: less than 5 years (107 cases), group 2: 5–10 years (120 cases), group 3: 10–16 years (98 cases). Results The incidence was 27 new cases/year (17–34 cases). There were 166 boys - 159 girls. Median age at diabetes onset was 7 years and 7months. Twenty three percent of the children had a familial history of diabetes type 1 significantly more frequent in group 1. Fifty two percent of all cases were diagnosed in the cold season. The age at introduction of cow milk in alimentation was less than 6 months in 54.4%. Cereals were introduced in alimentation at an age less than 3months in 12.3% of cases. Ketoacidosis revealed diabetes in 55.7% of cases, significantly more frequent in group 1 (66.3%), polyuria and polydipsia were more frequent in group 3 (98%). Hypoglycemia was more frequent in group 1. Conclusion Significant advances have been made in the clinical care, epidemiologic studies have an important on-going role to investigate the complex causes.

1211 Cyclosporine a in the Treatment of Resistant Childhood Nephrotic Syndrome

Background In children, idiopathic nephrotic syndrome is primarily treated using corticosteroids. When remission is not achieved, the administration of potent immunosuppressant therapy becomes imperative. Cyclosporine A (CsA) is reportedly associated with a higher incidence of remission in comparison with other immunosuppressive agents. The aim of our study is to evaluate the efficiency of cyclosporin A (CyA) therapy in 11 children treated with resistant nephrotic syndrome. Methods Eleven children enrolled in this study were all hospitalized with resistant nephrotic syndrome, aged 1 to 11 years (average 5.8 yrs) and included 7 males and 4 females. CyA was given to each patient with dosage of 5 mg/kg/day during the corticosteroid was diminished. The renwal biopsy was performed in all patients before the administration of CyA. Results Eleven children with resistant nephrotic syndrome of different pathological types were treated with CyA, including 3 cases of minimal change nephrotic syndrome (MCNS), 2 cases of mesangioproliferative glomerulonephritis (MsPGN), 1 case of extra membranous glomerulonephritis (EMGN) and 5 cases of focal segmental glomerular sclerosis (FSGS). Three patients got complete remission, seven patients developed chronic renal insufficiency and one had no change after four month treatment with CyA. The overall response rate was 27%. Patients with different renal pathological types showed different responses. The FSGS cases showed the lowest rate. Conclusion CyA has limited efficiency in patients with steroid-resistant nephrotic syndrome. CyA should be used cautiously because of the potential for CyA nephrotoxicity.