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Titolo:
Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
Autore:
De Kremer, RD; Paschini-Capra, A; Bacman, S; Argarana, C; Civallero, G; Kelley, RI; Guelbert, N; Latini, A; de Halac, IN; Giner-Ayala, A; Johnston, J; Proujansky, R; Gonzalez, I; Depetris-Boldini, C; Oller-Ramirez, A; Angaroni, C; Theaux, RA; Hliba, E; Juaneda, E;
Indirizzi:
Univ Nacl Cordoba, Fac Ciencias Med, Catedra Clin Pediat, CEMECO,Hosp Ninos, RA-5000 Cordoba, Argentina Univ Nacl Cordoba Cordoba Argentina RA-5000, RA-5000 Cordoba, Argentina Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol, Ctr Invest Quim BiolCordoba, RA-5000 Cordoba, Argentina Univ Nacl Cordoba Cordoba Argentina RA-5000 , RA-5000 Cordoba, Argentina Kennedy Krieger Inst, Baltimore, MD USA Kennedy Krieger Inst Baltimore MDUSA dy Krieger Inst, Baltimore, MD USA Johns Hopkins Univ, Baltimore, MD USA Johns Hopkins Univ Baltimore MD USA ohns Hopkins Univ, Baltimore, MD USA Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA Thomas Jefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA Du Pont Hosp Children, Dept Pediat, Wilmington, DE USA Du Pont Hosp Children Wilmington DE USA Dept Pediat, Wilmington, DE USA Du Pont Hosp Children, Res Dept, Wilmington, DE USA Du Pont Hosp ChildrenWilmington DE USA en, Res Dept, Wilmington, DE USA Univ Catolica Cordoba, Fac Ciencias Med, Dept Neuropatol, Cordoba, Argentina Univ Catolica Cordoba Cordoba Argentina Neuropatol, Cordoba, Argentina Univ Nacl Cordoba, Fac Ciencias Quim, Catedra Anat Patol, RA-5000 Cordoba,Argentina Univ Nacl Cordoba Cordoba Argentina RA-5000 l, RA-5000 Cordoba,Argentina Hosp Ninos, Serv Cardiovasc & Hemodinamia, Cordoba, Argentina Hosp Ninos Cordoba Argentina rdiovasc & Hemodinamia, Cordoba, Argentina
Titolo Testata:
AMERICAN JOURNAL OF MEDICAL GENETICS
fascicolo: 2, volume: 99, anno: 2001,
pagine: 83 - 93
SICI:
0148-7299(20010301)99:2<83:BSDANP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
LINKED CARDIOSKELETAL MYOPATHY; PROGRESSIVE MYOCLONUS EPILEPSIES; RESPIRATORY-CHAIN ABNORMALITIES; HUMAN SKELETAL-MUSCLE; RED FIBERS MERRF; 3-METHYLGLUTACONIC ACIDURIA; LACTIC-ACIDOSIS; TRNA(LEU(UUR)) GENE; EPISODES MELAS; LEIGH-SYNDROME;
Keywords:
mitochondrial cytopathy; MELAS; 3-methylglutaconic aciduria; Barth syndrome; cardiomyopathy; respiratory chain defects; ragged-red fibers; inborn errors of metabolism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: De Kremer, RD Univ Nacl Cordoba, Fac Ciencias Med, Catedra Clin Pediat, CEMECO,Hosp Ninos, Ferroviarior 1250, RA-5000 Cordoba, Argentina Univ Nacl Cordoba Ferroviarior 1250 Cordoba Argentina RA-5000
Citazione:
R.D. De Kremer et al., "Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)", AM J MED G, 99(2), 2001, pp. 83-93

Abstract

An Argentine male child died at 4.5 years of age of a lethal mitochondrialdisease associated with a MELAS mutation and a Earth syndrome-like presentation. The child had severe failure to thrive from the early months and forapproximately 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 S-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol, Detailed histopathologic evaluationof 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 apronounced and constant lactic acidosis, and abnormal urinary organic acidexcretion (unchanged in the fasting and postprandial states. In addition, in CSF there was a marked increase of lactate and P-hydroxybutyrate (P-HOE)and also a high systemic ratio HOB/acetoacetate, Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24%of compiler 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 Earth-like syndrome to the list of phenotypes with the MELAS mutation. (C) 2001 Wiley-Liss, Inc.

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Documento generato il 05/07/20 alle ore 23:01:12