Clinical, Molecular, and Computational Analysis in two cases with mitochondrial encephalomyopathy associated with SUCLG1 mutation in a consanguineous family.

Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (ß subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c.41T > C in the exon 1 at homozygous state. In-silico analysis revealed that this mutation substitutes a conserved methionine residue to a threonine at position 14 (p.M14T) located at the SUCLG1 protein mitochondrial targeting sequence. Moreover, these analysis predicted that this mutation alter stability structure and mitochondrial translocation of the protein. In Addition, a decrease in mtDNA copy number was revealed by real time PCR in the peripheral blood leukocytes in the two patients compared with controls.

Cribriform plate dehiscence with encephalomeningocele revealed by recurrent meningitis: A case report.

INTRODUCTION: Meningitis is a potentially life threatening illness. It requires prompt diagnosis and treatment. Recurrent meningitis needs detailed investigations to identify the underlying cause. OBSERVATION: We report a case of recurrent pneumococcal meningitis in a 9-year-old boy with an underlying congenital skull base abnormality. Brain computed tomography (CT) scan showed no obvious skull base defects. A magnetic resonance imaging (MRI) of the brain revealed a dehiscence of the cribriform plate with encephalomeningocele. The patient underwent an endoscopic repair of the bony defect and had not developed any new infections ever since. CONCLUSION: This case highlights the need to investigate recurrent bacterial meningitis with CT scan and MRI of the brain and skull base. Repair of these congenital skull base defects are mandatory to prevent the recurrence of meningitis.

Disseminated BCG infection revealing a severe combined immunodeficiency: A case report.

INTRODUCTION: Bacillus Calmette Guerin (BCG) vaccine, which is administered to all newborns in Tunisia, can lead to serious complications ranging from local disease to disseminated disease in a group of patients with primary immunodeficiency diseases. CASE REPORT: A 3-month-old boy presented with persistent fever, hepato-splenomegaly and multiple osteolytic lesions. He was diagnosed with severe combined immunodeficiency disease and disseminated BCG infection. Despite anti-tubercular therapy combined with intravenous immunoglobulin, the evolution was fatal. CONCLUSION: The case highlights the possible risk of such rare yet lethal complication of BCG vaccine. In suspected cases of primary immunodeficiency disease, inoculation of BCG should be postponed until appropriate screening tests exclude such diagnosis to prevent serious complications.

Pyogenic brain abscess in children: a Tunisian multi-center experience.

BACKGROUND: Brain abscess (BA) is an uncommon intracranial suppurative infectious disease, especially in children. Treatment involves surgery and prolonged courses of antibiotics. OBJECTIVES: Our study aimed to describe clinical characteristics of children with BA treated in middle Tunisian health centers. METHODS: A retrospective study lasting 19 years (1995-2014) was conducted in Tunisia middle region. Forty one children having radiologic abnormalities suggestive of BA and confirmed per operative lesions were included. Mycobacterial, parasitic or fungal abscesses were excluded. Medical records were analyzed for age, gender, presenting symptoms, predisposing factors, imaging, microbiology results, treatment and outcome. RESULTS: The mean age was 4.9 years. The most common clinical presentations were intracranial hypertension symptoms (87%). BA was diagnosed in 95.1% on the basis of cranial imaging. The majority of abscesses was supra-tentorial (92.6%). The most frequent etiology was loco-regional infections (63.4%). No predisposing factor was found in 17%. Intravenous antibiotics were given in all cases with surgical drainage in 63.4%,. Causative organisms were identified in 53.7%. The mortality rate was 24.3%. Age less than 2 years was the only statistically significant prognostic factor identified. CONCLUSION: Our study confirmed the severity of this pathology and underlined the importance of early diagnosis and management.

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes.

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C > T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C > T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1.

Infant acute myocarditis mimicking acute myocardial infarction.

Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis.

Giant cell hepatitis with autoimmune hemolytic anemia in a nine month old infant.

Giant cell hepatitis (GCH) with autoimmune hemolytic anemia is a rare entity, limited to young children, with an unknown pathogenesis. We report the case of 9-mo old who presented with fever, diarrhea and jaundice four days before hospitalization. Physical examination found pallor, jaundice and hepatosplenomegaly. The laboratory workup showed serum total bilirubin at 101 µmol/L, conjugated bilirubin at 84 µmol/L, hemolytic anemia, thrombocytopenia and immunoglobulin G (IgG) and anti-C3d positive direct Coombs' test. The antinuclear, anti-smooth muscle and liver kidney microsomes 1 non-organ specific autoantibodies, antiendomisium antibodies were negative. Serological assays for viral hepatitis B and C, cytomegalovirus, herpes simplex and Epstein Barr virus were negative. The association of acute liver failure, Evan's syndrome, positive direct Coomb's test of mixed type (IgG and C3) and the absence of organ and non-organ specific autoantibodies suggested the diagnosis of GCH. The diagnosis was confirmed by a needle liver biopsy. The patient was treated by corticosteroids, immunomodulatory therapy and azathioprine but died with septicemia.

Infant acute myocarditis mimicking acute myocardial infarction

Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis.