Mutational analysis in patients with neuromuscular disorders: Detection of mitochondrial deletion and double mutations in the MT-ATP6 gene.

Mitochondrial diseases encompass a wide variety of pathologies characterized by a dysfunction of the mitochondrial respiratory chain resulting in an energy deficiency. The respiratory chain consists of five multi-protein complexes providing coupling between nutrient oxidation and phosphorylation of ADP to ATP. In the present report, we studied mitochondrial genes of complex I, III, IV and V in 2 Tunisian patients with mitochondrial neuromuscular disorders. In the first patient, we detected the m.8392C>T variation (P136S) in the mitochondrial ATPase6 gene and the m.8527A>G transition at the junction MT-ATP6/MT-ATP8 which change the initiation codon AUG to GUG. The presence of these two variations in such an important gene could probably affect the ATP synthesis in the studied patient. In the second patient, we detected several known variations in addition to a mitochondrial deletion in the major arc of the mtDNA eliminating tRNA and respiratory chain protein genes. This deletion could be responsible of an inefficient translation leading to an inefficient mitochondrial protein synthesis in P2.

Clinical, immunological and genetic findings of a large tunisian series of major histocompatibility complex class II deficiency patients.

INTRODUCTION: Major histocompatibility complex class II (MHC-II) expression deficiency is a combined primary immunodeficiency leading to the impairment of the cellular and humoral immune responses. A majority of affected patients belong to consanguineous families particularly from the Maghreb, where a founder effect for a highly frequent mutation (named c.338-25_338del26) in the RFXANK gene was reported. Herein, we report the largest single Maghrebian country series of MHC-II deficient patients. PATIENTS AND METHODS: In Tunisia, among 551 PIDs diagnosed from 1993 to 2011, 54 had an MHC-II deficiency. The clinical features and immunological investigations were retrospectively analyzed in 34 children of them belonging to 28 kindred. The genetic study included the c.338-25_338del26 screening by the amplification of the affected region using polymerase chain reaction (PCR) followed by direct sequencing. RESULTS: Consanguinity was present in 22 out of 28 families. Mean age at the first infection was 6.1 months. Chronic diarrhea with failure to thrive and pulmonary infections were the most common manifestations occurring in 26 and 28 patients respectively. The most specific laboratory findings were the defect of MHC-II (HLA-DR) expression in all patients. The c.338-25_338del26 mutation was identified in 25 of them. CONCLUSION: In Maghrebian settings, pediatricians should definitely consider this diagnosis in the presence of an early onset of severe and recurrent infections of the respiratory and intestinal tracts, particularly protracted diarrhea with a failure to thrive. The founder effect for the c.338-25_338del26 mutation in the RFXANK gene is also confirmed, facilitating prenatal diagnosis as a preventive approach in the Tunisian affected families with severe forms, particularly in the context of limited access to bone marrow transplantation.

[Bardet - Biedl syndrome in the child. A study of 11 cases]. / Le syndrome de Bardet - Biedl chez l'enfant. Etude de 11 observations.

BACKGROUND: The syndrome of Bardet-Biedl is definite clinically by the association of obesity, polydactyly, pigmentary retinopathy, hypogonadism and backwardness. AIM: To study the epidemiologic, clinical, biological, genetic, therapeutic and evolutionary characteristic of our patients. METHODS: We carried out a retrospective study concerning 11 hospitalized children and/or follow-ups with the service of pediatry of the CHU Hédi Chaker of Sfax for syndrome of Bardet-Biedl during a period of 21 years (1987-2007). RESULTS: The obesity was constant among all patients, polydactyly was found in 9 cases, the fall of night vision in 7 cases. The hypogonadism was constant among all our boys. The bottom of eye was practised among 9 patients, it showed a pigmentary aspect of retinopathy among 8 patients. The electroretinogram was done in 10 patients, it showed a pigmentary retinopathy in all the cases. The radiological exploration of the urinary tract made it possible to identify morphological anomalies in 3 cases. The genetic study concerned the families of one of our patients and it allowed the identification of a new gene BBS8 at one of the families. Treatment was only symptomatic. After 6 years an average retreat, we noted an aggravation of obesity (9cas) and visual deficit (7cas). Only one patient evolved to the chronic renal insufficiency. CONCLUSION: The syndrome of Bardet-Biedl is a hereditary disease characterized by a genetic heterogeneity. The diversity of the systemic attacks defining this syndrome is a source of several handicaps: blindness, backwardness and obesity. The forecast is conditioned by the renal attack of or the interest of an early tracking and genetic council.

[Type I Crigler Najjar syndrome in Tunisia: a study of 30 cases]. / La Maladie De Crigler Najjar De Type I En Tunisie : Etude De 30 Observations.

BACKGROUND: Crigler-Najjar syndrome is a rare metabolic disorder characterized by severe unconjugated hyperbilirubinemia resulting in deficiency of bilirubin uridine diphosphate (UDP) glucuronosyltransferase activity in the liver. AIM: To study the clinical, genetic therapeutic aspects and the outcome of Crigler Najjar type 1 in Tunisia. METHODS: This is a retrospective report of Crigler Najjar cases who were hospitalised in pediatric department of Hédi Chaker hospital during 21 years (from 1st January to 31 December 2006). RESULTS: Our study included 30 cases of Crigler-Najjar syndrome; there were 10 females and 20 males (sex ratio = 2). The mean age of our patients was 41 days (4 days - 9 months). All patients were presented with intense jaundice. Sixteen patients had neurologic disorders since admission. Genetic analysis was performed in 9 patients; we identified the same mutation in all cases: -C1070>G in exon 3 of the UDP glucuronyl transferase. Concerning therapeutic measurements, conventional phototherapy was used in all patients. A fatal out come was observed in 28 case; they died of kernicterus. CONCLUSION: Crigler-Najjar syndrome is a serious disorder which, when not treated, ultimately leads to brain damage (bilirubin encephalopathy) and death. That's why we must promote prenatal diagnosis and genetic council especially because of the big frequency of consanguinity in our country.

[Persistent forms of cow's milk allergy. Report of 6 cases]. / Les formes persistantes de l'allergie aux protéines du lait de vache. A propos de 6 cas.

BACKGROUND: Cow's milk allergy is defined as reproducible adverse reaction to a food protein antigen which is immune medieted. About 80 to 90 % become clinically tolerated within the first three year of live. The aim of this study is to evaluate the clinical, immunological and evolutive characteristics of the 10 % to 20 % of persistent form of cow's milk allergy. METHODS: This study included six persistent form of cow's milk allergy (2 boys and 4 girls). The provocation challenge test according to Rance recommendation, have been made from 6 months to one year. RESULTS: 4/6 infants with persistent cow's milk allergy have an atopic familial disease. Clinical presentation changed over time at once symptoms were preventely gastrointestinal, at the end there was an increased frequency of atopic disease (asthma: 4/6 infants) CONCLUSION: Persistent form of cow's milk allergy are characterized by considerable importance of familial atopic disease; change in cow's milk allergy manifestations over time and more prolonged delay between cow's milk persistent consumption and manifestations of symptoms.