RESUMO
An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.
Assuntos
DNA Mitocondrial/genética , Síndrome MELAS/genética , Mutação Puntual , Ácido 3-Hidroxibutírico/sangue , Ácidos/líquido cefalorraquidiano , Ácidos/urina , Argentina , Biópsia , Pré-Escolar , Transporte de Elétrons , Humanos , Lactatos/sangue , Lactatos/líquido cefalorraquidiano , Síndrome MELAS/diagnóstico , Masculino , Mitocôndrias/enzimologia , Músculo Esquelético/patologia , Músculo Esquelético/ultraestrutura , Fenótipo , SíndromeRESUMO
One of conjoined thoracopagus twins, with separate hearts and a common pericardial sack, presented with respiratory distress because of a persistent arterial duct causing congestive heart failure in the neonatal period. Surgical ligation of the duct was performed prior to subsequent separation, with an excellent outcome.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Tórax/anormalidades , Persistência do Tronco Arterial/cirurgia , Gêmeos Unidos/cirurgia , Ecocardiografia Doppler , Feminino , Seguimentos , Humanos , Recém-Nascido , Ligadura/métodos , Imageamento por Ressonância Magnética , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Resultado do Tratamento , Persistência do Tronco Arterial/complicações , Persistência do Tronco Arterial/diagnóstico , Gêmeos Unidos/patologia , Ultrassonografia Pré-Natal/métodosRESUMO
We report a 6-year-old girl with superoinferior ventricles, criss-cross atrioventricular (AV) relationships with solitus atria, a D-loop, L-transposition of the great arteries, subpulmonary stenosis, but without a ventricular septal defect (VSD). The diagnosis was made by echocardiographic examination and was strengthened by cardiac catheterization and angiocardiography. Balloon atrial septostomy in the neonatal period and a modified Blalock-Taussig shunt at the age of 16 months were performed to alleviate hypoxia. Following the shunt operation, the clinical condition of the patient deteriorated with progressive cardiac enlargement, congestive heart failure, and tricuspid regurgitation. We assume that the absence of a VSD contributed to this deterioration. Subsequent improvement was obtained with balloon enlargement of the atrial septal defect and a bidirectional Glenn anastomosis.