MCID: MTC020
MIFTS: 48

Mitochondrial Complex Ii Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Mitochondrial Complex Ii Deficiency

MalaCards integrated aliases for Mitochondrial Complex Ii Deficiency:

Name: Mitochondrial Complex Ii Deficiency 53 12 49 71 36 28 13 41 14 69
Succinate Coq Reductase Deficiency 53 49 71
Isolated Mitochondrial Respiratory Chain Complex Ii Deficiency 12 55
Mitochondrial Respiratory Chain Complex Ii Deficiency 53 49
Complex 2 Mitochondrial Respiratory Chain Deficiency 49 71
Isolated Succinate-Coenzyme Q Reductase Deficiency 12 55
Isolated Succinate-Ubiquinone Reductase Deficiency 12 55
Isolated Succinate-Coq Reductase Deficiency 12 55
Complex Ii Mitochondrial Respiratory Chain Deficiency 71
Sdh-Defective Infantile Leukoencephalopathy 71
Succinate-Coenzyme Q Reductase Deficiency 69
Succinate Dehydrogenase Deficiency 49
Mt-C2d 71

Characteristics:

Orphanet epidemiological data:

55
isolated succinate-coq reductase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in first year of life


HPO:

31
mitochondrial complex ii deficiency:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Complex Ii Deficiency

NIH Rare Diseases : 49 Complex II deficiency is a mitochondrial disease. Mitochondria are specialized compartments in cells that create more than 90% of the energy needed by the body. In mitochondrial diseases, the mitochondria don't work correctly resulting in less energy in the cell, cell injury and cell death. The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood. Complex II deficiency can be caused by mutations in the SDHA, SDHB, SDHD, or SDHAF1 genes. In many cases the underlying gene mutations cannot be identified. Complex II deficiency is inherited in an autosomal recessive fashion. Complex II deficiency gene mutation carriers may be at an increased risk for certain cancers. Last updated: 4/15/2015

MalaCards based summary : Mitochondrial Complex Ii Deficiency, also known as succinate coq reductase deficiency, is related to leigh syndrome and paraganglioma, and has symptoms including ataxia, seizures and myoclonus. An important gene associated with Mitochondrial Complex Ii Deficiency is SDHAF1 (Succinate Dehydrogenase Complex Assembly Factor 1), and among its related pathways/superpathways are Citrate cycle (TCA cycle) and Oxidative phosphorylation. The drugs Azacitidine and Antimetabolites have been mentioned in the context of this disorder. Affiliated tissues include kidney, brain and liver, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

OMIM : 53 Mitochondrial complex II deficiency is an autosomal recessive disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013). (252011)

UniProtKB/Swiss-Prot : 71 Mitochondrial complex II deficiency: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome.

Disease Ontology : 12 A mitochondrial metabolism disease characerized by a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. It has material basis in homozygous or compound heterozygous mutation in the nuclear-encoded SDHA gene on chromosome 5p, the nuclear-encoded SDHAF1 gene on chromosome 19q, or the nuclear-encoded SDHD gene on chromosome 11q23.

Related Diseases for Mitochondrial Complex Ii Deficiency

Diseases related to Mitochondrial Complex Ii Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 34)
# Related Disease Score Top Affiliating Genes
1 leigh syndrome 30.5 ENSG00000255292 SDHA SDHAF1 SDHB SDHD
2 paraganglioma 27.7 SDHA SDHAF2 SDHB SDHC SDHD
3 pheochromocytoma 27.7 ENSG00000255292 SDHA SDHB SDHC SDHD
4 spastic quadriplegia 10.1 SDHAF1 SDHD
5 cowden syndrome 3 10.1 ENSG00000255292 SDHD
6 quadriplegia 10.0 SDHA SDHD
7 cerebellopontine angle tumor 10.0 ENSG00000255292 SDHD
8 seminal vesicle tumor 9.9 SDHA SDHB
9 glomus tumor 9.9 SDHB SDHD
10 blood group, i system 9.9
11 multiple endocrine neoplasia, type iia 9.8 SDHB SDHD
12 leukodystrophy 9.7
13 encephalomyopathy 9.7
14 multiple endocrine neoplasia, type i 9.6 SDHB SDHD
15 kearns-sayre syndrome 9.5 ENSG00000255292 SDHA SDHAF1 SDHD
16 multiple endocrine neoplasia 9.4 SDHB SDHC
17 chondroma 9.4 SDHB SDHC SDHD
18 sporadic pheochromocytoma 9.4 SDHB SDHC SDHD
19 von hippel-lindau syndrome 9.4 SDHB SDHC SDHD
20 cowden disease 9.4 SDHB SDHC SDHD
21 neurofibromatosis, type iv, of riccardi 9.4 SDHB SDHC SDHD
22 carney triad 9.1 SDHA SDHB SDHC SDHD
23 paragangliomas 1 9.1 ENSG00000255292 SDHB SDHC SDHD
24 adrenal medulla cancer 9.1 SDHAF2 SDHB SDHC SDHD
25 extra-adrenal pheochromocytoma 9.1 SDHAF2 SDHB SDHC SDHD
26 gastrointestinal stromal tumor 9.1 SDHA SDHB SDHC SDHD
27 paraganglioma and gastric stromal sarcoma 9.1 ENSG00000255292 SDHB SDHC SDHD
28 phaeochromocytoma 9.1 SDHAF2 SDHB SDHC SDHD
29 lymphatic system disease 9.1 ENSG00000255292 SDHB SDHC SDHD
30 endocrine gland cancer 9.1 ENSG00000255292 SDHB SDHC SDHD
31 persistent generalized lymphadenopathy 8.8 SDHA SDHAF2 SDHB SDHC SDHD
32 hereditary paraganglioma-pheochromocytoma syndromes 8.8 SDHA SDHAF2 SDHB SDHC SDHD
33 lymph node disease 8.8 SDHA SDHAF2 SDHB SDHC SDHD
34 neural crest tumor 8.4 ENSG00000255292 SDHA SDHAF2 SDHB SDHC SDHD

Graphical network of the top 20 diseases related to Mitochondrial Complex Ii Deficiency:



Diseases related to Mitochondrial Complex Ii Deficiency

Symptoms & Phenotypes for Mitochondrial Complex Ii Deficiency

Symptoms via clinical synopsis from OMIM:

53
NeurologicCentralNervousSystem:
ataxia
seizures
myoclonus
dystonia
spasticity
more
HeadAndNeckEyes:
ophthalmoplegia
ptosis
nystagmus
optic atrophy
pigmentary retinopathy
more
CardiovascularHeart:
hypertrophic cardiomyopathy
dilated cardiomyopathy
left ventricular noncompaction

GrowthOther:
poor growth

LaboratoryAbnormalities:
decreased activity of mitochondrial complex ii (succinate dehydrogenase)
mildly increased serum lactate

MuscleSoftTissue:
muscle weakness
exercise intolerance
ragged red fibers seen on muscle biopsy
hypotonia, neonatal
abnormal mitochondria with paracrystalline inclusions seen on muscle biopsy
more
GrowthHeight:
short stature

Skeletal:
joint contractures

MetabolicFeatures:
lactic acidosis may occur with stress or infection


Clinical features from OMIM:

252011

Human phenotypes related to Mitochondrial Complex Ii Deficiency:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 seizures 31 HP:0001250
3 myoclonus 31 HP:0001336
4 muscle weakness 31 HP:0001324
5 dystonia 31 HP:0001332
6 ophthalmoplegia 31 HP:0000602
7 ptosis 31 HP:0000508
8 nystagmus 31 HP:0000639
9 spasticity 31 HP:0001257
10 hyperreflexia 31 HP:0001347
11 developmental regression 31 HP:0002376
12 visual impairment 31 HP:0000505
13 optic atrophy 31 HP:0000648
14 neonatal hypotonia 31 HP:0001319
15 short stature 31 HP:0004322
16 flexion contracture 31 HP:0001371
17 cognitive impairment 31 HP:0100543
18 hypertrophic cardiomyopathy 31 HP:0001639
19 babinski sign 31 HP:0003487
20 increased serum lactate 31 HP:0002151
21 ragged-red muscle fibers 31 HP:0003200
22 increased intramyocellular lipid droplets 31 HP:0012240
23 dilated cardiomyopathy 31 HP:0001644
24 exercise intolerance 31 HP:0003546
25 pigmentary retinopathy 31 HP:0000580
26 progressive leukoencephalopathy 31 HP:0006980
27 leukoencephalopathy 31 HP:0002352
28 left ventricular noncompaction 31 HP:0030682
29 abnormal mitochondria in muscle tissue 31 HP:0008316
30 stress/infection-induced lactic acidosis 31 HP:0004897
31 decreased activity of mitochondrial complex ii 31 HP:0008314

UMLS symptoms related to Mitochondrial Complex Ii Deficiency:


muscle weakness, seizures, ophthalmoplegia, myoclonus, muscle spasticity, ataxia

GenomeRNAi Phenotypes related to Mitochondrial Complex Ii Deficiency according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.17 SDHC
2 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.17 SDHC SDHD
3 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.17 SDHC
4 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.17 SDHC
5 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.17 SDHC SDHD

Drugs & Therapeutics for Mitochondrial Complex Ii Deficiency

Drugs for Mitochondrial Complex Ii Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Azacitidine Approved, Investigational Phase 2 320-67-2 9444
2 Antimetabolites Phase 2
3 Antimetabolites, Antineoplastic Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer Recruiting NCT03165721 Phase 2 SGI-110 (guadecitabine)

Search NIH Clinical Center for Mitochondrial Complex Ii Deficiency

Cochrane evidence based reviews: mitochondrial complex ii deficiency

Genetic Tests for Mitochondrial Complex Ii Deficiency

Genetic tests related to Mitochondrial Complex Ii Deficiency:

# Genetic test Affiliating Genes
1 Mitochondrial Complex Ii Deficiency 28 SDHA SDHAF1 SDHD

Anatomical Context for Mitochondrial Complex Ii Deficiency

MalaCards organs/tissues related to Mitochondrial Complex Ii Deficiency:

38
Kidney, Brain, Liver, Heart

Publications for Mitochondrial Complex Ii Deficiency

Articles related to Mitochondrial Complex Ii Deficiency:

# Title Authors Year
1
A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency. ( 26008905 )
2015
2
Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency. ( 24367056 )
2013
3
Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. ( 22972948 )
2012
4
Anesthetic management for a child with mitochondrial complex II deficiency. ( 18613941 )
2008
5
The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. ( 16288654 )
2005

Variations for Mitochondrial Complex Ii Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex Ii Deficiency:

71
# Symbol AA change Variation ID SNP ID
1 SDHAF1 p.Arg55Pro VAR_058097 rs137853193
2 SDHAF1 p.Gly57Arg VAR_058098 rs137853192
3 SDHA p.Gly555Glu VAR_016879 rs137852768
4 SDHD p.Glu69Lys VAR_074105 rs202198133
5 SDHD p.Asp92Gly VAR_074106 rs786205436

ClinVar genetic disease variations for Mitochondrial Complex Ii Deficiency:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 SDHA NM_004168.3(SDHA): c.1571C> T (p.Ala524Val) single nucleotide variant Pathogenic rs137852767 GRCh37 Chromosome 5, 251126: 251126
2 SDHA NM_004168.3(SDHA): c.1A> C (p.Met1Leu) single nucleotide variant Pathogenic rs1061517 GRCh37 Chromosome 5, 218471: 218471
3 SDHA NM_004168.3(SDHA): c.1664G> A (p.Gly555Glu) single nucleotide variant Pathogenic rs137852768 GRCh37 Chromosome 5, 251453: 251453
4 SDHA NM_004168.3(SDHA): c.1526C> T (p.Ser509Leu) single nucleotide variant Pathogenic rs397514541 GRCh37 Chromosome 5, 240566: 240566
5 SDHD NM_003002.3(SDHD): c.205G> A (p.Glu69Lys) single nucleotide variant Pathogenic/Likely pathogenic rs202198133 GRCh38 Chromosome 11, 112088902: 112088902
6 SDHD NM_003002.3(SDHD): c.275A> G (p.Asp92Gly) single nucleotide variant Pathogenic rs786205436 GRCh38 Chromosome 11, 112088972: 112088972
7 SDHAF1 NM_001042631.2(SDHAF1): c.169G> C (p.Gly57Arg) single nucleotide variant Pathogenic rs137853192 GRCh37 Chromosome 19, 36486345: 36486345
8 SDHAF1 NM_001042631.2(SDHAF1): c.164G> C (p.Arg55Pro) single nucleotide variant Pathogenic rs137853193 GRCh37 Chromosome 19, 36486340: 36486340
9 SDHA NM_004168.3(SDHA): c.457-2_457delAGC deletion Likely pathogenic rs878854632 GRCh38 Chromosome 5, 225881: 225883
10 SDHA NM_004168.3(SDHA): c.1054C> T (p.Arg352Ter) single nucleotide variant Pathogenic rs746165168 GRCh38 Chromosome 5, 233635: 233635
11 SDHA NM_004168.3(SDHA): c.1432+1G> C single nucleotide variant Likely pathogenic rs878854628 GRCh37 Chromosome 5, 236715: 236715
12 SDHA NM_004168.3(SDHA): c.762_770+17del26 deletion Likely pathogenic rs1064792987 GRCh38 Chromosome 5, 228325: 228350
13 SDHA NM_004168.3(SDHA): c.1615dupA (p.Ile539Asnfs) duplication Pathogenic GRCh38 Chromosome 5, 251055: 251055
14 SDHA NM_004168.3(SDHA): c.985C> T (p.Arg329Ter) single nucleotide variant Pathogenic rs771328239 GRCh38 Chromosome 5, 233566: 233566

Expression for Mitochondrial Complex Ii Deficiency

Search GEO for disease gene expression data for Mitochondrial Complex Ii Deficiency.

Pathways for Mitochondrial Complex Ii Deficiency

Pathways related to Mitochondrial Complex Ii Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Citrate cycle (TCA cycle) hsa00020
2 Oxidative phosphorylation hsa00190

GO Terms for Mitochondrial Complex Ii Deficiency

Cellular components related to Mitochondrial Complex Ii Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.55 ENSG00000255292 SDHA SDHB SDHC SDHD
2 mitochondrion GO:0005739 9.5 ENSG00000255292 SDHA SDHAF1 SDHAF2 SDHB SDHC
3 mitochondrial envelope GO:0005740 9.32 ENSG00000255292 SDHD
4 respiratory chain complex II GO:0045273 9.26 SDHB SDHC
5 mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) GO:0005749 9.02 ENSG00000255292 SDHA SDHB SDHC SDHD

Biological processes related to Mitochondrial Complex Ii Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.55 ENSG00000255292 SDHA SDHB SDHC SDHD
2 electron transport chain GO:0022900 9.5 SDHA SDHB SDHC
3 aerobic respiration GO:0009060 9.43 SDHB SDHC
4 tricarboxylic acid cycle GO:0006099 9.43 ENSG00000255292 SDHA SDHAF2 SDHB SDHC SDHD
5 respiratory electron transport chain GO:0022904 9.4 SDHA SDHB
6 succinate metabolic process GO:0006105 9.37 SDHA SDHB
7 mitochondrial respiratory chain complex II assembly GO:0034553 9.26 SDHAF1 SDHAF2
8 mitochondrial electron transport, succinate to ubiquinone GO:0006121 9.02 ENSG00000255292 SDHA SDHAF2 SDHC SDHD

Molecular functions related to Mitochondrial Complex Ii Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 9.5 ENSG00000255292 SDHC SDHD
2 ubiquinone binding GO:0048039 9.43 ENSG00000255292 SDHB SDHD
3 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.37 SDHA SDHC
4 electron transfer activity GO:0009055 9.35 ENSG00000255292 SDHA SDHB SDHC SDHD
5 succinate dehydrogenase activity GO:0000104 9.33 SDHA SDHC SDHD
6 succinate dehydrogenase (ubiquinone) activity GO:0008177 8.92 ENSG00000255292 SDHA SDHB SDHD

Sources for Mitochondrial Complex Ii Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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