Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)

dc.creatorDodelson De Kremer, Raquel
dc.creatorPaschini Capra, Ana
dc.creatorBacman, Sandra
dc.creatorArgaraña, Carlos
dc.creatorCivallero, Gabriel
dc.creatorKelley, Richard I.
dc.creatorGuelbert, Norberto
dc.creatorLatini, Alexandra
dc.creatorNoher de Halac, Inés
dc.creatorGiner Ayala, Alicia
dc.creatorJohnston, Jennifer
dc.creatorProujansky, Roy
dc.date2001-12-31
dc.date.accessioned2023-08-30T17:09:06Z
dc.date.available2023-08-30T17:09:06Z
dc.identifierhttp://pa.bibdigital.ucc.edu.ar/3930/1/A_DodelsondeKremer_PaschiniCapra_Bacman_Argara%C3%B1a_Civallero_Kelley_Guelbert_Latini_NoherdeHalac_GinerAyala_Johnston_Proujansky.pdf
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8539659
dc.descriptionAn 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 β-hydroxybutyrate (β-HOB) and also a high systemic ratio β-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.
dc.descriptionFil: Dodelson De Kremer, Raquel. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Paschini Capra, Ana. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Bacman, Sandra. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Argaraña, Carlos. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Civallero, Gabriel. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Kelley, Richard I. Kennedy Krieger Institute and Johns Hopkins University, Baltimore, MD, United States
dc.descriptionFil: Guelbert, Norberto. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Latini, Alexandra. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Noher de Halac, Inés. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina
dc.descriptionFil: Giner Ayala, Alicia. Universidad Nacional de Córdoba; Argentina
dc.descriptionFil: Johnston, Jennifer. Departments of Pediatrics and Research, Du Pont Hospital for Children, Wilmington, Delaware Jefferson Medical College, Philadelphia, PA, United States
dc.descriptionFil: Proujansky, Roy. Departments of Pediatrics and Research, Du Pont Hospital for Children, Wilmington, Delaware Jefferson Medical College, Philadelphia, PA, United States
dc.formatapplication/pdf
dc.languagespa
dc.relationhttp://pa.bibdigital.ucc.edu.ar/3930/
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1002/1096-8628(2001)9999:9999<::AID-AJMG1136>3.0.CO;2-X
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.sourceDodelson De Kremer, Raquel ORCID: https://orcid.org/0000-0003-4365-3661 <https://orcid.org/0000-0003-4365-3661>, Paschini Capra, Ana, Bacman, Sandra ORCID: https://orcid.org/0000-0001-8701-6010 <https://orcid.org/0000-0001-8701-6010>, Argaraña, Carlos ORCID: https://orcid.org/0000-0002-6169-3344 <https://orcid.org/0000-0002-6169-3344>, Civallero, Gabriel, Kelley, Richard I. ORCID: https://orcid.org/0000-0001-9906-1345 <https://orcid.org/0000-0001-9906-1345>, Guelbert, Norberto ORCID: https://orcid.org/0000-0003-3860-4750 <https://orcid.org/0000-0003-3860-4750>, Latini, Alexandra ORCID: https://orcid.org/0000-0003-4255-3589 <https://orcid.org/0000-0003-4255-3589>, Noher de Halac, Inés ORCID: https://orcid.org/0000-0003-2930-9282 <https://orcid.org/0000-0003-2930-9282>, Giner Ayala, Alicia, Johnston, Jennifer and Proujansky, Roy (2001) Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation). American Journal of Medical Genetics, 99 (2). pp. 83-93. ISSN 0148-7299
dc.subjectR Medicina (General)
dc.titleBarth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/acceptedVersion


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