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

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 d...

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Autores principales: Dodelson De Kremer, Raquel, Paschini Capra, Ana, Bacman, Sandra, Argaraña, Carlos, Civallero, Gabriel, Kelley, Richard I., Guelbert, Norberto, Latini, Alexandra, Noher de Halac, Inés, Giner Ayala, Alicia, Johnston, Jennifer, Proujansky, Roy
Formato: Artículo
Lenguaje:Español
Publicado: 2001
Materias:
R Medicina (General)
Acceso en línea:http://pa.bibdigital.ucc.edu.ar/3930/1/A_DodelsondeKremer_PaschiniCapra_Bacman_Argara%C3%B1a_Civallero_Kelley_Guelbert_Latini_NoherdeHalac_GinerAyala_Johnston_Proujansky.pdf
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Producción Académica Universidad Católica de Córdoba (UCCor) de Universidad Católica de Córdoba
id I38-R144-3930
record_format dspace
spelling I38-R144-39302025-04-09T22:06:10Z http://pa.bibdigital.ucc.edu.ar/3930/ Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation) Dodelson De Kremer, Raquel Paschini Capra, Ana Bacman, Sandra Argaraña, Carlos Civallero, Gabriel Kelley, Richard I. Guelbert, Norberto Latini, Alexandra Noher de Halac, Inés Giner Ayala, Alicia Johnston, Jennifer Proujansky, Roy R Medicina (General) 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 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. 2001-12-31 info:eu-repo/semantics/article info:eu-repo/semantics/closedAccess application/pdf spa http://pa.bibdigital.ucc.edu.ar/3930/1/A_DodelsondeKremer_PaschiniCapra_Bacman_Argara%C3%B1a_Civallero_Kelley_Guelbert_Latini_NoherdeHalac_GinerAyala_Johnston_Proujansky.pdf Dodelson 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 info:eu-repo/semantics/altIdentifier/doi/10.1002/1096-8628(2001)9999:9999<::AID-AJMG1136>3.0.CO;2-X
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic R Medicina (General)
spellingShingle R Medicina (General)
Dodelson De Kremer, Raquel
Paschini Capra, Ana
Bacman, Sandra
Argaraña, Carlos
Civallero, Gabriel
Kelley, Richard I.
Guelbert, Norberto
Latini, Alexandra
Noher de Halac, Inés
Giner Ayala, Alicia
Johnston, Jennifer
Proujansky, Roy
Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
topic_facet R Medicina (General)
description 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 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.
format Artículo
author Dodelson De Kremer, Raquel
Paschini Capra, Ana
Bacman, Sandra
Argaraña, Carlos
Civallero, Gabriel
Kelley, Richard I.
Guelbert, Norberto
Latini, Alexandra
Noher de Halac, Inés
Giner Ayala, Alicia
Johnston, Jennifer
Proujansky, Roy
author_facet Dodelson De Kremer, Raquel
Paschini Capra, Ana
Bacman, Sandra
Argaraña, Carlos
Civallero, Gabriel
Kelley, Richard I.
Guelbert, Norberto
Latini, Alexandra
Noher de Halac, Inés
Giner Ayala, Alicia
Johnston, Jennifer
Proujansky, Roy
author_sort Dodelson De Kremer, Raquel
title Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
title_short Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
title_full Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
title_fullStr Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
title_full_unstemmed Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)
title_sort barth's syndrome-like disorder: a new phenotype with a maternally inherited a3243g substitution of mitochondrial dna (melas mutation)
publishDate 2001
url http://pa.bibdigital.ucc.edu.ar/3930/1/A_DodelsondeKremer_PaschiniCapra_Bacman_Argara%C3%B1a_Civallero_Kelley_Guelbert_Latini_NoherdeHalac_GinerAyala_Johnston_Proujansky.pdf
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