Table 1.
Clinical presentation of previously described patients with combined respiratory complex deficiency and mutations in nuclear genes affecting mitochondrial protein synthesis
| Gene (number of cases) | Family history | Age at symptom onset/death |
Clinical presentation |
Additional symptoms | Histology RRF/ COX- fibres/other | Reference | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| M | N | H | L | LA | ||||||
| Nuclear components of the mitochondrial translation machinery | ||||||||||
| EFG1 (2) | Consanguinity, affected sibling | Birth/27 d | + | + | – | + | + | Intrauterine growth retardation, corpus callosum hypoplasia, cystic brain lesion | Normal muscle | Coenen et al., 2004 |
| EFG1 (2) | Affected sibling | Birth/9 d | + | + | DA | + | + | Intrauterine growth retardation, dysmorphy | Many COX-fibres, no RRF | Antonicka et al., 2006 |
| EFG1 (1) | 3 w/16 m | + | + | – | – | + | Dysmorphy, microcephaly | SDH+/COX-fibres, lipid accumulation | Valente et al., 2007 | |
| EFTu (1) | 2 d/14 m | + | + | +/– | + | + | Macrocystic leukodystrophy, polymicrogyria | nd | Valente et al., 2007 | |
| EFTs (1) | Consanguinity | Birth/ 7 w | + | + | DA | – | + | Rhabdomyolysis, epilepsy | nd(?) | Smeitink et al., 2006 |
| EFTs (1) | Consanguinity | 2 d/7 w | + | – | + | – | + | Low urinary output, hyponatraemia | Generalized COX- | Smeitink et al., 2006 |
| C12orf65 (3) | Consanguinity | 1 y/>22 y | + | + | – | – | + | Leigh syndrome, optic atrophy, ophthalmoplegia | nd | Antonicka et al., 2010 |
| Ribosomal protein genes | ||||||||||
| MRPS16 (1) | Consanguinity | 1 d/9 d | + | + | DA | + | + | Corpus callosum agenesia, dysmorphy | nd | Miller et al., 2004 |
| MRPS22 (2) | Consanguinity, affected sibling | Birth/22 d | + | – | + | – | + | Subcutaneous oedema, tubulopathy | nd | Saada et al., 2007 |
| tRNA modifying genes and tRNA synthetases | ||||||||||
| PUS1 (6) | Consanguinity 2 families | + | – | – | – | + | Severe sideroblastic anaemia, mental retardation, dysmorphic features | Mitochondrial myopathy | Bykhovskaya et al., 2004 | |
| PUS1 (2) | Consanguinity, affected sibling | 6 m/12 y | + | – | – | – | + | Growth retardation, severe sideroblastic anaemia, cognitive impairment, dysmorphy | COX-/RRF, myopathy | Fernandez-Vizarra et al., 2007 |
| RARS2 (3) | Consanguinity | Birth/16 m | + | + | – | – | +/– | Cerebellar and vermian hypoplasia. microcephaly | nd | Edvardson et al., 2007 |
| DARS2 (several) | Consanguinity | – | + | – | – | – | Leucoencephalopathy with brainstem and spinal cord involvement | Normal?/nd | Scheper et al., 2007 | |
| DARS2 (8) | – | + | – | – | – | Leucoencephalopathy with brainstem and spinal cord involvement | Normal?/nd | Isohanni et al., 2010 | ||
| TRMU (13) | Consanguinity | 2–4 m | – | – | – | + | + | Isolated reversible hepatopathy | Normal muscle, mitochondrial pathology in liver | Elpeleg 2009 |
| YARS2 (3) | Consanguinity | 10 w/>24 y | + | – | + | – | + | Severe sideroblastic anaemia, cardiomyopathy | RRF/COX-fibres | Riley et al., 2010 |
DA = open ductus arteriosus; H = heart disease; L = liver involvement; LA = lactic acidosis; M = muscle; N = neurological symptoms; d = day; w = week; y = year; m = month; RRF = ragged red fibres; nd = not determined.