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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 7202589, 11 pages
Research Article

Combined Respiratory Chain Deficiency and UQCC2 Mutations in Neonatal Encephalomyopathy: Defective Supercomplex Assembly in Complex III Deficiencies

1Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
2Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8010 Graz, Austria
3Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany
4Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany
5Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria
6Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8010 Graz, Austria
7Department of Human Genetics, Medical University of Graz, 8010 Graz, Austria
8Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, 5020 Salzburg, Austria
9Department for Paediatric and Adolescent Medicine, Schwabing Hospital, Technische Universität München, 80804 Munich, Germany

Correspondence should be addressed to René G. Feichtinger

Received 26 January 2017; Revised 22 March 2017; Accepted 4 June 2017; Published 19 July 2017

Academic Editor: Maik Hüttemann

Copyright © 2017 René G. Feichtinger 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.


Vertebrate respiratory chain complex III consists of eleven subunits. Mutations in five subunits either mitochondrial (MT-CYB) or nuclear (CYC1, UQCRC2, UQCRB, and UQCRQ) encoded have been reported. Defects in five further factors for assembly (TTC19, UQCC2, and UQCC3) or iron-sulphur cluster loading (BCS1L and LYRM7) cause complex III deficiency. Here, we report a second patient with UQCC2 deficiency. This girl was born prematurely; pregnancy was complicated by intrauterine growth retardation and oligohydramnios. She presented with respiratory distress syndrome, developed epileptic seizures progressing to status epilepticus, and died at day 33. She had profound lactic acidosis and elevated urinary pyruvate. Exome sequencing revealed two homozygous missense variants in UQCC2, leading to a severe reduction of UQCC2 protein. Deficiency of complexes I and III was found enzymatically and on the protein level. A review of the literature on genetically distinct complex III defects revealed that, except TTC19 deficiency, the biochemical pattern was very often a combined respiratory chain deficiency. Besides complex III, typically, complex I was decreased, in some cases complex IV. In accordance with previous observations, the presence of assembled complex III is required for the stability or assembly of complexes I and IV, which might be related to respirasome/supercomplex formation.