ABSTRACT
A síndrome de Kearns-Sayre é uma patologia rara, que acarreta piora da qualidade de vida; caracteriza-se por oftalmoplegia externa progressiva, fraqueza muscular e distúrbios na condução cardíaca. A entidade integra um grupo de desordens do metabolismo mitocondrial, denominadas miopatias mitocondriais ou citopatias mitocondriais.
Kearns-Sayres syndrome is a rare pathology which leads to a worse quality of life of the individual; it is characterized by progressive external ophthalmoplegia, muscular weakness, and cardiac conduction defects. The disease belongs to a group of mitochondrial metabolic disorders, named mitochondrial myopathies of mitochondrial cytopathies.
Subject(s)
Humans , Female , Cardiomyopathies/etiology , DNA, Mitochondrial/metabolism , Muscle Weakness/etiology , Mitochondrial Myopathies/diagnosis , Mitochondrial Myopathies/therapy , Ophthalmoplegia, Chronic Progressive External/etiology , Kearns-Sayre Syndrome/complications , Kearns-Sayre Syndrome/diagnosis , Kearns-Sayre Syndrome/therapy , Genetic Therapy , Antioxidants/therapeutic use , Quality of LifeABSTRACT
Mitochondrial myopathy is the term applied to a clinically and biochemically heterogeneous group of disorders which have multisystem involvement. The concept was introduced by Luft in 1962. These are due to genetic defects in the respiratory chain enzymes which are detected by histochemical, immunohistochemical stains, molecular biological studies and ultrastructural studies on muscle biopsy. Classification of the disorders can be genetic, based on defects of respiratory enzyme complexes or on the basis of the clinical syndromes. Due to the extremely variable clinical presentations of these disorders, a complete clinical and laboratory workup involving strict diagnostic criteria is essential.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , DNA, Mitochondrial/genetics , Electron Transport/genetics , Humans , Infant , Infant, Newborn , Mitochondria, Muscle/enzymology , Mitochondrial Myopathies/diagnosis , Multienzyme Complexes/geneticsABSTRACT
Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. Plasma acylcarnitine via tandem mass spectrometry was reported normal; however, urine organic acids via gas liquid chromatography and mass spectrometry demonstrated characteristic metabolites consistent with MCADD. Case 3. Carnitine deficiency, systemic primary. (CDSP) (OMIM 212140) A one-year-old girl with progressive dyspnea since birth and a history of parental consanguinity. Severe dilated cardiomyopathy with episodes of cardiac decompensations, hepatomegaly, anemia, generalized hypotonia, but no hypoglycemia were demonstrated prior to cardiac arrest. Extremely low carnitine level noted in dried blood spots via tandem mass spectrometry.
Subject(s)
3-Hydroxyacyl CoA Dehydrogenases/deficiency , Cardiomyopathy, Hypertrophic/diagnosis , Carnitine/deficiency , Fatal Outcome , Fatty Acids/metabolism , Female , Humans , Infant , Infant, Newborn , Lipid Metabolism, Inborn Errors/complications , Lipid Peroxidation , Male , Mitochondrial Diseases/diagnosis , Mitochondrial Myopathies/diagnosis , Prognosis , Risk Assessment , Severity of Illness Index , Spectrometry, Mass, Electrospray Ionization , ThailandABSTRACT
The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years). Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes), three had MERRF (myoclonic epilepsy and ragged red fibre myopathy), three cases had KSS (Kearns-Sayre Syndrome) and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%). Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , India , Kearns-Sayre Syndrome/diagnosis , MELAS Syndrome/diagnosis , MERRF Syndrome/diagnosis , Male , Mitochondrial Myopathies/diagnosisSubject(s)
Humans , Female , Child, Preschool , Mitochondrial Myopathies/rehabilitation , Neurodegenerative Diseases , Physical Therapy Specialty , Palliative Care , Developmental Disabilities , Ethics, Professional , Mitochondrial Myopathies/diagnosis , Neurodegenerative Diseases , Parent-Child Relations , Quality of LifeABSTRACT
Mitochondrial myopathy is a group of multisytemic disease, variable in the age at onset, frequency, clinical data, evolution and prognosis. It results from nuclear or mitochondrial DNA mutation or from defective interaction between nuclear and mitochondrial DNA. The transmission of this mitochondrial myopathy is exlusively maternal. Sometimes the mutationns are born in the maternal ovule, or early in the embryonal life. The diagnosis is suspected on clinical manifestations and is confirmed by existence of ragged - red - fibers in the muscular biopsy, and especially, by molecular study which discovers the mutation of mitochondrial DNA. The treatment is often disappointing, however some specific measures are necessary to improve the quality of patients life
Subject(s)
Humans , Mitochondrial Myopathies/diagnosis , Mitochondrial Myopathies/drug therapy , MERRF Syndrome , Muscle Fibers, Fast-Twitch/pathology , DNA, Mitochondrial , MutationABSTRACT
Defects in structures or functions of mitochondria, mainly involving the oxidative phosphorylation, mitochondrial biogenesis and other metabolic pathways have been shown to be associated with a wide spectrum of clinical phenotypes. The ubiquitous nature of mitochondria and their unique genetic features contribute to the clinical, biochemical and genetic heterogenecity of mitochondrial diseases. This article focuses on the recent advances in the field of mitochondrial disorders with respect to the consequences for an advanced clinical and genetic diagnostics. In addition, an overview on recently identified genetic defects and their pathogenic molecular mechanisms are given.
Subject(s)
Adult , Aged , Aging/physiology , Diabetes Mellitus/diagnosis , Female , Heart Failure/diagnosis , Humans , Male , Middle Aged , Mitochondria/genetics , Mitochondrial Myopathies/diagnosis , Neurodegenerative Diseases/diagnosis , PrognosisABSTRACT
Objetivo: Analisar o teste de esforço cardiopulmonar (TECP) no diagnóstico de miopatias. Métodos: 27 pacientes com miopatia realizaram TECP (protocolo de bicicleta em rampa, máximo, interrompido por sintoma). Resultados: Pacientes distróficos e pacientes com mitocondriopatias mostraram diferenças significativas em relaçao aos controles para as variáveis potência do trabalho desenvolvido (watt) e pico do consumo de oxigênio (VO2máx). Pacientes com mitocondriopatias mostraram diminuiçao significativa do limiar anaeróbio em relaçao aos controles, além de elevaçao dos valores do quociente respiratório (QR) do pico do exercício em relaçao aos demais grupos. Conclusoes: TECP pode ser útil na avaliaçao evolutiva do grau de limitaçao física dos pacientes com miopatia. As variáveis potência do trabalho desenvolvido, VO2 máx, limiar anaeróbio e QR do pico do exercício podem sugerir o diagnóstico de miopatia e seus subtipos, excluindo quadros psicológicos.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Metabolism, Inborn Errors/physiopathology , Muscular Diseases/physiopathology , Exercise Test , Glycogen Storage Disease/diagnosis , Glycogen Storage Disease/physiopathology , Metabolism, Inborn Errors/diagnosis , Mitochondrial Myopathies/diagnosis , Mitochondrial Myopathies/physiopathology , Muscular Diseases/diagnosis , Muscular Dystrophies/diagnosis , Muscular Dystrophies/physiopathologyABSTRACT
Neste trabalho os autores descrevem três casos de miopatia do multicore na mesma família. O caso 1 corresponde a um paciente de 77 anos, com fraqueza e atrofias proximais, hipotonia e hiporreflexia profunda globais. Estudos da cnduçäo nervosa sensitiva e motora foram normais nos quatro membros. A eletromiografia revelou padräo miopático, com atividade espontânea frequênte, tipo fibrilaçöes e ondas agudas positivas. As reaçöes histoquímicas mostraram alteraçöes oxidativas típicas de miopatia do multicore. Os casos 2 e 3 correspondem a filho e filha do paciente 1, respectivamente. Estes dois casos eram assintomáticos, mas apresentavam discretas alteraçöes eletromiográficas e à biópsia de músculo. Os três pacientes ilustram a grande variabilidade clínica desta entidade