TY  - JOUR
A1  - Braczynski, Anne Kristin
A1  - Vlaho, Stefan
A1  - Müller, Klaus
A1  - Wittig, Ilka
A1  - Blank, Anna-Eva
A1  - Tews, Dominique Suzanne
A1  - Drott, Ulrich
A1  - Kleinle, Stephanie
A1  - Abicht, Angela
A1  - Horvath, Rita
A1  - Plate, Karl
A1  - Stenzel, Werner
A1  - Goebel, Hans Hilmar
A1  - Schulze-Bonhage, Andreas
A1  - Harter, Patrick Nikolaus
A1  - Kieslich, Matthias
A1  - Mittelbronn, Michel Guy André
T1  - ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment
T2  - BioMed research international
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50659
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-506593
SN  - 2314-6141
SN  - 2314-6133
N1  - 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.
VL  - 2015
IS  - Art. 462592
SP  - 1
EP  - 10
PB  - Hindawi
CY  - New York [u. a.]
ER  -