GTR Home > Conditions/Phenotypes > Mitochondrial complex I deficiency

Summary

Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including NDUFV1 (161015), NDUFV2 (600532), NDUFS1 (157655), NDUFS2 (602985), NDUFS3 (603846), NDUFS4 (602694), NDUFS6 (603848), NDUFS7 (601825), NDUFS8 (602141), NDUFA2 (602137), NDUFA11 (612638), NDUFAF3 (612911), NDUFA10 (603835), NDUFB3 (603839), NDUFB8 (602140), NDUFB9 (601445), and the complex I assembly genes NDUFAF2 (609653), NDUFAF4 (611776), NDUFAF5 (612360), NUBPL (613621), NDUFAF1 (606934), TMEM126B (615533), TIMMDC1 (615534), and NDUFA13 (609435). The disorder can also be caused by mutation in other nuclear-encoded genes, including FOXRED1 (613622), ACAD9 (611103; see 611126), and MTFMT (611766; see 256000). X-linked inheritance is observed with mutations in the NDUFA1 (300078) and NDUFB11 (300403) genes. Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome (256000). Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085). [from OMIM]

Available tests

176 tests are in the database for this condition.

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Genes See tests for all associated and related genes

  • Also known as: FP634, H17, FOXRED1
    Summary: FAD dependent oxidoreductase domain containing 1

  • Also known as: CI-MWFE, MWFE, ZNF183, NDUFA1
    Summary: NADH:ubiquinone oxidoreductase subunit A1

  • Also known as: B14.7, CI-B14.7, NDUFA11
    Summary: NADH:ubiquinone oxidoreductase subunit A11

  • Also known as: B16.6, CDA016, CGI-39, GRIM-19, GRIM19, NDUFA13
    Summary: NADH:ubiquinone oxidoreductase subunit A13

  • Also known as: CGI-65, CGI65, CIA30, NDUFAF1
    Summary: NADH:ubiquinone oxidoreductase complex assembly factor 1

  • Also known as: B17.2L, MMTN, NDUFA12L, mimitin, NDUFAF2
    Summary: NADH:ubiquinone oxidoreductase complex assembly factor 2

  • Also known as: 2P1, C3orf60, E3-3, NDUFAF3
    Summary: NADH:ubiquinone oxidoreductase complex assembly factor 3

  • Also known as: C6orf66, HRPAP20, HSPC125, My013, bA22L21.1, NDUFAF4
    Summary: NADH:ubiquinone oxidoreductase complex assembly factor 4

  • Also known as: C20orf7, bA526K24.2, dJ842G6.1, NDUFAF5
    Summary: NADH:ubiquinone oxidoreductase complex assembly factor 5

  • Also known as: CI-ESSS, ESSS, NP17.3, Np15, P17.3, NDUFB11
    Summary: NADH:ubiquinone oxidoreductase subunit B11

  • Also known as: B12, CI-B12, NDUFB3
    Summary: NADH:ubiquinone oxidoreductase subunit B3

  • Also known as: B22, CI-B22, LYRM3, UQOR22, NDUFB9
    Summary: NADH:ubiquinone oxidoreductase subunit B9

  • Also known as: CI-75Kd, CI-75k, PRO1304, NDUFS1
    Summary: NADH:ubiquinone oxidoreductase core subunit S1

  • Also known as: CI-49, NDUFS2
    Summary: NADH:ubiquinone oxidoreductase core subunit S2

  • Also known as: CI-30, NDUFS3
    Summary: NADH:ubiquinone oxidoreductase core subunit S3

  • Also known as: AQDQ, CI-18, CI-18 kDa, CI-AQDQ, NDUFS4
    Summary: NADH:ubiquinone oxidoreductase subunit S4

  • Also known as: CI-13kA, CI-13kD-A, CI13KDA, NDUFS6
    Summary: NADH:ubiquinone oxidoreductase subunit S6

  • Also known as: CI-51K, CI51KD, UQOR1, NDUFV1
    Summary: NADH:ubiquinone oxidoreductase core subunit V1

  • Also known as: CI-24k, NDUFV2
    Summary: NADH:ubiquinone oxidoreductase core subunit V2

  • Also known as: C14orf127, IND1, huInd1, NUBPL
    Summary: nucleotide binding protein like

  • Also known as: C3orf1, TIMMDC1
    Summary: translocase of inner mitochondrial membrane domain containing 1

  • Also known as: HT007, TMEM126B
    Summary: transmembrane protein 126B

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