Anne Kristin Braczynski, Stefan Vlaho, Klaus Müller, Ilka Wittig, Anna-Eva Blank, Dominique Suzanne Tews, Ulrich Drott, Stephanie Kleinle, Angela Abicht, Rita Horvath, Karl Plate, Werner Stenzel, Hans Hilmar Goebel, Andreas Schulze-Bonhage, Patrick Nikolaus Harter, Matthias Kieslich, Michel Guy André Mittelbronn
- TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment.
MetadatenAuthor: | Anne Kristin BraczynskiORCiDGND, Stefan Vlaho, Klaus Müller, Ilka WittigORCiD, Anna-Eva Blank, Dominique Suzanne Tews, Ulrich Drott, Stephanie Kleinle, Angela Abicht, Rita Horvath, Karl PlateGND, Werner Stenzel, Hans Hilmar Goebel, Andreas Schulze-BonhageORCiDGND, Patrick Nikolaus HarterORCiDGND, Matthias Kieslich, Michel Guy André MittelbronnORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-506593 |
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DOI: | https://doi.org/10.1155/2015/462592 |
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ISSN: | 2314-6141 |
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ISSN: | 2314-6133 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26550569 |
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Parent Title (English): | BioMed research international |
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Publisher: | Hindawi |
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Place of publication: | New York [u. a.] |
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Contributor(s): | Michelangelo Mancuso |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2015 |
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Year of first Publication: | 2015 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2019/08/12 |
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Volume: | 2015 |
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Issue: | Art. 462592 |
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Page Number: | 11 |
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First Page: | 1 |
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Last Page: | 10 |
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Note: | Copyright © 2015 Anne K. Braczynski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
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HeBIS-PPN: | 453725848 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 3.0 |
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