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Mitochondrial complex III deficiency(MC3DN1)

MedGen UID:
377658
•Concept ID:
C1852372
•
Disease or Syndrome
Synonyms: Complex 3 mitochondrial respiratory chain deficiency; Deficiency of mitochondrial complex III; MC3DN1
SNOMED CT: Deficiency of ubiquinone cytochrome c oxidoreductase (709414007); Deficiency of mitochondrial complex III (709414007); Deficiency of isolated CoQ cytochrome c reductase (709414007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Mitochondrial inheritance
MedGen UID:
165802
•Concept ID:
C0887941
•
Genetic Function
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy).
Autosomal recessive inheritance (Orphanet)
Mitochondrial inheritance (Orphanet)
 
Monarch Initiative: MONDO:0015448
Orphanet: ORPHA1460

Definition

Isolated complex III deficiency is a rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a wide spectrum of clinical manifestations ranging from isolated myopathy or transient hepatopathy to severe multisystem disorder (that may include hypotonia, failure to thrive, psychomotor delay, cardiomyopathy, encephalopathy, renal tubulopathy, hearing impairment, lactic acidosis, hypoglycemia and other signs and symptoms). [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMitochondrial complex III deficiency

Recent clinical studies

Etiology

Phenotypic variation of TTC19-deficient mitochondrial complex III deficiency: a case report and literature review.
Mordaunt DA, Jolley A, Balasubramaniam S, Thorburn DR, Mountford HS, Compton AG, Nicholl J, Manton N, Clark D, Bratkovic D, Friend K, Yu S
Am J Med Genet A 2015 Jun;167(6):1330-6. Epub 2015 Apr 21 doi: 10.1002/ajmg.a.36968. PMID: 25899669
A Japanese case of cerebellar ataxia, spastic paraparesis and deep sensory impairment associated with a novel homozygous TTC19 mutation.
Kunii M, Doi H, Higashiyama Y, Kugimoto C, Ueda N, Hirata J, Tomita-Katsumoto A, Kashikura-Kojima M, Kubota S, Taniguchi M, Murayama K, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N, Tanaka F
J Hum Genet 2015 Apr;60(4):187-91. Epub 2015 Feb 5 doi: 10.1038/jhg.2015.7. PMID: 25652355
Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.
Wolfe LA, He M, Vockley J, Payne N, Rhead W, Hoppel C, Spector E, Gernert K, Gibson KM
J Inherit Metab Dis 2010 Dec;33 Suppl 3(0 3):S481-7. Epub 2010 Nov 19 doi: 10.1007/s10545-010-9246-8. PMID: 21088898Free PMC Article
Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation.
Schuelke M, Krude H, Finckh B, Mayatepek E, Janssen A, Schmelz M, Trefz F, Trijbels F, Smeitink J
Ann Neurol 2002 Mar;51(3):388-92. doi: 10.1002/ana.10151. PMID: 11891837

Diagnosis

LYRM7-associated mitochondrial complex III deficiency with non-cavitating leukoencephalopathy and stroke-like episodes.
Alfattal R, Alfarhan M, Algaith AM, Albash B, Elshafie RM, Alshammari A, Alahmad A, Dashti F, Alsafi R, Alsharhan H
Am J Med Genet A 2023 May;191(5):1401-1411. Epub 2023 Feb 9 doi: 10.1002/ajmg.a.63143. PMID: 36757047
Bi-Allelic UQCRFS1 Variants Are Associated with Mitochondrial Complex III Deficiency, Cardiomyopathy, and Alopecia Totalis.
Gusic M, Schottmann G, Feichtinger RG, Du C, Scholz C, Wagner M, Mayr JA, Lee CY, Yépez VA, Lorenz N, Morales-Gonzalez S, Panneman DM, Rötig A, Rodenburg RJT, Wortmann SB, Prokisch H, Schuelke M
Am J Hum Genet 2020 Jan 2;106(1):102-111. Epub 2019 Dec 26 doi: 10.1016/j.ajhg.2019.12.005. PMID: 31883641Free PMC Article
Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation.
Miyake N, Yano S, Sakai C, Hatakeyama H, Matsushima Y, Shiina M, Watanabe Y, Bartley J, Abdenur JE, Wang RY, Chang R, Tsurusaki Y, Doi H, Nakashima M, Saitsu H, Ogata K, Goto Y, Matsumoto N
Hum Mutat 2013 Mar;34(3):446-52. Epub 2013 Jan 29 doi: 10.1002/humu.22257. PMID: 23281071
Radiological and electroencephalographic findings in mitochondrial complex III deficiency.
Díaz-Negrillo A, Sanz Santaeufemia F
Acta Neurol Taiwan 2012 Dec;21(4):192-3. PMID: 23329552
Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies.
Ghezzi D, Arzuffi P, Zordan M, Da Re C, Lamperti C, Benna C, D'Adamo P, Diodato D, Costa R, Mariotti C, Uziel G, Smiderle C, Zeviani M
Nat Genet 2011 Mar;43(3):259-63. Epub 2011 Jan 30 doi: 10.1038/ng.761. PMID: 21278747

Therapy

Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C.
Toscano A, Fazio MC, Vita G, Cannavó S, Bresolin N, Bet L, Prelle A, Barbiroli B, Iotti S, Zaniol P
J Neurol 1995 Mar;242(4):203-9. doi: 10.1007/BF00919592. PMID: 7798118

Prognosis

Differential proteomic profiling unveils new molecular mechanisms associated with mitochondrial complex III deficiency.
Marín-Buera L, García-Bartolomé A, Morán M, López-Bernardo E, Cadenas S, Hidalgo B, Sánchez R, Seneca S, Arenas J, Martín MA, Ugalde C
J Proteomics 2015 Jan 15;113:38-56. Epub 2014 Sep 18 doi: 10.1016/j.jprot.2014.09.007. PMID: 25239759Free PMC Article
Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation.
Miyake N, Yano S, Sakai C, Hatakeyama H, Matsushima Y, Shiina M, Watanabe Y, Bartley J, Abdenur JE, Wang RY, Chang R, Tsurusaki Y, Doi H, Nakashima M, Saitsu H, Ogata K, Goto Y, Matsumoto N
Hum Mutat 2013 Mar;34(3):446-52. Epub 2013 Jan 29 doi: 10.1002/humu.22257. PMID: 23281071
Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.
Wolfe LA, He M, Vockley J, Payne N, Rhead W, Hoppel C, Spector E, Gernert K, Gibson KM
J Inherit Metab Dis 2010 Dec;33 Suppl 3(0 3):S481-7. Epub 2010 Nov 19 doi: 10.1007/s10545-010-9246-8. PMID: 21088898Free PMC Article
Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation.
Tuppen HA, Fehmi J, Czermin B, Goffrini P, Meloni F, Ferrero I, He L, Blakely EL, McFarland R, Horvath R, Turnbull DM, Taylor RW
Mol Genet Metab 2010 Aug;100(4):345-8. Epub 2010 Apr 24 doi: 10.1016/j.ymgme.2010.04.010. PMID: 20472482

Clinical prediction guides

Phenotypic variation of TTC19-deficient mitochondrial complex III deficiency: a case report and literature review.
Mordaunt DA, Jolley A, Balasubramaniam S, Thorburn DR, Mountford HS, Compton AG, Nicholl J, Manton N, Clark D, Bratkovic D, Friend K, Yu S
Am J Med Genet A 2015 Jun;167(6):1330-6. Epub 2015 Apr 21 doi: 10.1002/ajmg.a.36968. PMID: 25899669
Differential proteomic profiling unveils new molecular mechanisms associated with mitochondrial complex III deficiency.
Marín-Buera L, García-Bartolomé A, Morán M, López-Bernardo E, Cadenas S, Hidalgo B, Sánchez R, Seneca S, Arenas J, Martín MA, Ugalde C
J Proteomics 2015 Jan 15;113:38-56. Epub 2014 Sep 18 doi: 10.1016/j.jprot.2014.09.007. PMID: 25239759Free PMC Article
Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation.
Miyake N, Yano S, Sakai C, Hatakeyama H, Matsushima Y, Shiina M, Watanabe Y, Bartley J, Abdenur JE, Wang RY, Chang R, Tsurusaki Y, Doi H, Nakashima M, Saitsu H, Ogata K, Goto Y, Matsumoto N
Hum Mutat 2013 Mar;34(3):446-52. Epub 2013 Jan 29 doi: 10.1002/humu.22257. PMID: 23281071
Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.
Wolfe LA, He M, Vockley J, Payne N, Rhead W, Hoppel C, Spector E, Gernert K, Gibson KM
J Inherit Metab Dis 2010 Dec;33 Suppl 3(0 3):S481-7. Epub 2010 Nov 19 doi: 10.1007/s10545-010-9246-8. PMID: 21088898Free PMC Article
Mitochondrial complex III deficiency associated with a homozygous mutation in UQCRQ.
Barel O, Shorer Z, Flusser H, Ofir R, Narkis G, Finer G, Shalev H, Nasasra A, Saada A, Birk OS
Am J Hum Genet 2008 May;82(5):1211-6. Epub 2008 Apr 24 doi: 10.1016/j.ajhg.2008.03.020. PMID: 18439546Free PMC Article

Recent systematic reviews

A TTC19 mutation associated with progressive movement disorders and peripheral neuropathy: Case report and systematic review.
Xuan X, Ruan J, Wu C, Gao Y, Li L, Lei X
CNS Neurosci Ther 2024 Mar;30(3):e14425. Epub 2023 Nov 6 doi: 10.1111/cns.14425. PMID: 37927170Free PMC Article

Supplemental Content

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