ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment
Joint Authors
Harter, Patrick N.
Mittelbronn, Michel
Braczynski, Anne K.
Vlaho, Stefan
Müller, Klaus
Wittig, Ilka
Blank, Anna-Eva
Tews, Dominique S.
Drott, Ulrich
Kleinle, Stephanie
Abicht, Angela
Horvath, Rita
Plate, Karl H.
Stenzel, Werner
Goebel, Hans H.
Schulze, Andreas
Kieslich, Matthias
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-10-13
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Braczynski, Anne K.& Vlaho, Stefan& Müller, Klaus& Wittig, Ilka& Blank, Anna-Eva& Tews, Dominique S.…[et al.]. 2015. ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment. BioMed Research International،Vol. 2015, no. 2015, pp.1-10.
https://search.emarefa.net/detail/BIM-1055573
Modern Language Association (MLA)
Braczynski, Anne K.…[et al.]. ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment. BioMed Research International No. 2015 (2015), pp.1-10.
https://search.emarefa.net/detail/BIM-1055573
American Medical Association (AMA)
Braczynski, Anne K.& Vlaho, Stefan& Müller, Klaus& Wittig, Ilka& Blank, Anna-Eva& Tews, Dominique S.…[et al.]. ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-10.
https://search.emarefa.net/detail/BIM-1055573
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1055573