MC4DN2
MCID: MTC208
MIFTS: 33

Mitochondrial Complex Iv Deficiency, Nuclear Type 2 (MC4DN2)

Categories: Cardiovascular diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal diseases

Aliases & Classifications for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

MalaCards integrated aliases for Mitochondrial Complex Iv Deficiency, Nuclear Type 2:

Name: Mitochondrial Complex Iv Deficiency, Nuclear Type 2 57
Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency 1 57 72 13
Cytochrome C Oxidase Deficiency, Fatal Infantile, with Cardioencephalomyopathy 57 6
Mitochondrial Complex Ii Deficiency, Nuclear Type 4 57 6
Cemcox1 57 72
Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency 1; Cemcox1 57
Cardioencephalomyopathy, Fatal Infantile, Due to Cytochrome C Oxidase Deficiency 70
Fatal Infantile Cardioencephalomyopathy Due to Cytochrome C Oxidase Deficiency 1 12
Cytochrome C Oxidase Deficiency with Fatal Infantile Cardioencephalomyopathy 72
Mc4dn2 57
Mc2dn4 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
death usually in infancy or early childhood
onset in infancy (range birth to 12 months)
onset of cardiomyopathy may occur several months after birth


HPO:

31
mitochondrial complex iv deficiency, nuclear type 2:
Onset and clinical course death in infancy congenital onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080357
OMIM® 57 604377 619224
OMIM Phenotypic Series 57 PS220110 PS252011
MedGen 41 C1858424
UMLS 70 C1858424

Summaries for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

OMIM® : 57 Mitochondrial complex IV deficiency nuclear type 2 (MC4DN2) is an autosomal recessive multisystem metabolic disorder characterized by the onset of symptoms at birth or in the first weeks or months of life. Affected individuals have severe hypotonia, often associated with feeding difficulties and respiratory insufficiency necessitating tube feeding and mechanical ventilation. The vast majority of patients develop hypertrophic cardiomyopathy in the first days or weeks of life, which usually leads to death in infancy or early childhood. Patients also show neurologic abnormalities, including developmental delay, nystagmus, fasciculations, dystonia, EEG changes, and brain imaging abnormalities compatible with a diagnosis of Leigh syndrome (see 256000). There may also be evidence of systemic involvement with hepatomegaly and myopathy, although neurogenic muscle atrophy is more common and may resemble spinal muscular atrophy type I (SMA1; 253300). Serum lactate is increased, and laboratory studies show decreased mitochondrial complex IV protein and activity levels in various tissues, including heart and skeletal muscle. Most patients die in infancy of cardiorespiratory failure (summary by Papadopoulou et al., 1999). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110. (604377) (Updated 05-Apr-2021)

MalaCards based summary : Mitochondrial Complex Iv Deficiency, Nuclear Type 2, also known as cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, is related to myopia 6 and myopia, and has symptoms including dyspnea An important gene associated with Mitochondrial Complex Iv Deficiency, Nuclear Type 2 is SCO2 (Synthesis Of Cytochrome C Oxidase 2). Affiliated tissues include spinal cord, skeletal muscle and thalamus, and related phenotypes are global developmental delay and feeding difficulties in infancy

Disease Ontology : 12 A fatal infantile cardioencephalomyopathy due to cytochrome c oxidase deficiency that has material basis in compound heterozygous mutation in the SCO2 gene on chromosome 22q13.

UniProtKB/Swiss-Prot : 72 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1: A disorder characterized by hypotonia, developmental delay, hypertrophic cardiomyopathy, lactic acidosis, gliosis, neuronal loss in basal ganglia, brainstem and spinal cord, and cytochrome c oxidase deficiency.

Related Diseases for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Graphical network of the top 20 diseases related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2:



Diseases related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Symptoms & Phenotypes for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Human phenotypes related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 HP:0001263
2 feeding difficulties in infancy 31 HP:0008872
3 hypertrophic cardiomyopathy 31 HP:0001639
4 increased serum lactate 31 HP:0002151
5 increased csf lactate 31 HP:0002490
6 lactic acidosis 31 HP:0003128
7 respiratory distress 31 HP:0002098
8 generalized hypotonia 31 HP:0001290
9 neuronal loss in central nervous system 31 HP:0002529
10 limited extraocular movements 31 HP:0007941
11 neuronal loss in basal ganglia 31 HP:0200147
12 basal ganglia gliosis 31 HP:0006999
13 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
nystagmus
limited extraocular movements

Neurologic Central Nervous System:
global developmental delay
dystonia
seizures (in some patients)
eeg abnormalities
leigh syndrome
more
Cardiovascular Heart:
hypertrophic cardiomyopathy

Metabolic Features:
lactic acidosis

Head And Neck Mouth:
high-arched palate

Respiratory:
respiratory insufficiency
stridor
mechanical ventilation

Muscle Soft Tissue:
myopathy
fasciculations
hypotonia, severe
neurogenic changes seen on emg
decreased cytochrome c oxidase activity seen on muscle biopsy

Laboratory Abnormalities:
increased serum lactate
increased csf lactate
mitochondrial respiratory complex iv deficiency in patient tissues

Abdomen Gastrointestinal:
feeding difficulties
tube feeding

Neurologic Peripheral Nervous System:
sensorimotor axonal or demyelinating polyneuropathy

Clinical features from OMIM®:

604377 619224 (Updated 05-Apr-2021)

UMLS symptoms related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2:


dyspnea

Drugs & Therapeutics for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Search Clinical Trials , NIH Clinical Center for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Genetic Tests for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Anatomical Context for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

MalaCards organs/tissues related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2:

40
Spinal Cord, Skeletal Muscle, Thalamus

Publications for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Articles related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2:

(show all 18)
# Title Authors PMID Year
1
Phenotypic consequences of a novel SCO2 gene mutation. 57 6
18924171 2008
2
Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype. 6 57
14994243 2004
3
Reversion of hypertrophic cardiomyopathy in a patient with deficiency of the mitochondrial copper binding protein Sco2: is there a potential effect of copper? 57 6
14970747 2004
4
Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease. 57 6
12020273 2002
5
Homozygosity (E140K) in SCO2 causes delayed infantile onset of cardiomyopathy and neuropathy. 6 57
11673586 2001
6
Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency. 57 6
10749987 2000
7
Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. 6 57
10545952 1999
8
Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: Case report and review of the literature. 6
32124427 2020
9
Leukoencephalopathy due to Complex II Deficiency and Bi-Allelic SDHB Mutations: Further Cases and Implications for Genetic Counselling. 6
27604842 2017
10
Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy. 6
26642834 2016
11
Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance. 6
26925370 2015
12
Mutations in SCO2 are associated with autosomal-dominant high-grade myopia. 6
23643385 2013
13
Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. 6
22972948 2012
14
Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma. 6
20592014 2010
15
Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in Sco2. 57
19837698 2010
16
Somatic SDHB mutation in an extraadrenal pheochromocytoma. 6
17634472 2007
17
Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. 6
16326995 2006
18
Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality. 57
15210538 2004

Variations for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

ClinVar genetic disease variations for Mitochondrial Complex Iv Deficiency, Nuclear Type 2:

6 (show all 45)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*880G>A SNV Pathogenic 5678 rs74315510 GRCh37: 22:50962684-50962684
GRCh38: 22:50524255-50524255
2 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*363G>A SNV Pathogenic 5679 rs80358232 GRCh37: 22:50962167-50962167
GRCh38: 22:50523738-50523738
3 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*526G>A SNV Pathogenic 5680 rs28937598 GRCh37: 22:50962330-50962330
GRCh38: 22:50523901-50523901
4 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*769G>A SNV Pathogenic 5682 rs74315512 GRCh37: 22:50962573-50962573
GRCh38: 22:50524144-50524144
5 NCAPH2 , SCO2 NM_005138.3(SCO2):c.179_188dup (p.Ile63fs) Duplication Pathogenic 5683 GRCh37: 22:50962652-50962653
GRCh38: 22:50524223-50524224
6 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*639C>T SNV Pathogenic 5684 rs28937868 GRCh37: 22:50962443-50962443
GRCh38: 22:50524014-50524014
7 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*930C>T SNV Pathogenic 5685 rs121908508 GRCh37: 22:50962734-50962734
GRCh38: 22:50524305-50524305
8 SDHB NM_003000.3(SDHB):c.143A>T SNV Pathogenic 39584 rs202101384 GRCh37: 1:17371313-17371313
GRCh38: 1:17044818-17044818
9 SDHB NM_003000.3(SDHB):c.769C>G (p.Leu257Val) SNV Pathogenic 584582 rs761350633 GRCh37: 1:17345450-17345450
GRCh38: 1:17018955-17018955
10 SDHB NM_003000.2(SDHB):c.689G>A (p.Arg230His) SNV Pathogenic 142637 rs587782604 GRCh37: 1:17349179-17349179
GRCh38: 1:17022684-17022684
11 SDHB NM_003000.3(SDHB):c.304G>A (p.Ala102Thr) SNV Pathogenic 822717 rs777578399 GRCh37: 1:17355214-17355214
GRCh38: 1:17028719-17028719
12 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*619C>T SNV Pathogenic 5681 rs74315511 GRCh37: 22:50962423-50962423
GRCh38: 22:50523994-50523994
13 NCAPH2 , SCO2 NM_005138.3(SCO2):c.256C>T (p.Gln86Ter) SNV Pathogenic 1034155 GRCh37: 22:50962585-50962585
GRCh38: 22:50524156-50524156
14 NCAPH2 , SCO2 NM_005138.3(SCO2):c.2T>C (p.Met1Thr) SNV Likely pathogenic 800843 rs1603441682 GRCh37: 22:50962839-50962839
GRCh38: 22:50524410-50524410
15 NCAPH2 , SCO2 NM_005138.3(SCO2):c.226C>T (p.Leu76=) SNV Uncertain significance 900387 GRCh37: 22:50962615-50962615
GRCh38: 22:50524186-50524186
16 NCAPH2 , SCO2 NM_005138.3(SCO2):c.173G>A (p.Arg58Gln) SNV Uncertain significance 900447 GRCh37: 22:50962668-50962668
GRCh38: 22:50524239-50524239
17 NCAPH2 , SCO2 NM_005138.3(SCO2):c.723C>T (p.Tyr241=) SNV Uncertain significance 800057 rs375345044 GRCh37: 22:50962118-50962118
GRCh38: 22:50523689-50523689
18 SCO2 NM_005138.2(SCO2):c.-51C>T SNV Uncertain significance 342129 rs886057631 GRCh37: 22:50963938-50963938
GRCh38: 22:50525509-50525509
19 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*1033G>C SNV Uncertain significance 342128 rs747642461 GRCh37: 22:50962837-50962837
GRCh38: 22:50524408-50524408
20 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*793T>C SNV Uncertain significance 342125 rs765425160 GRCh37: 22:50962597-50962597
GRCh38: 22:50524168-50524168
21 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*875G>A SNV Uncertain significance 342127 rs139545104 GRCh37: 22:50962679-50962679
GRCh38: 22:50524250-50524250
22 SCO2 NM_005138.2(SCO2):c.-83A>G SNV Uncertain significance 342131 rs886057632 GRCh37: 22:50963970-50963970
GRCh38: 22:50525541-50525541
23 SCO2 NM_005138.2(SCO2):c.-114G>C SNV Uncertain significance 342132 rs554814235 GRCh37: 22:50964001-50964001
GRCh38: 22:50525572-50525572
24 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*299C>G SNV Uncertain significance 342123 rs200605042 GRCh37: 22:50962103-50962103
GRCh38: 22:50523674-50523674
25 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*761T>C SNV Uncertain significance 342124 rs886057630 GRCh37: 22:50962565-50962565
GRCh38: 22:50524136-50524136
26 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*659C>T SNV Uncertain significance 215127 rs150880212 GRCh37: 22:50962463-50962463
GRCh38: 22:50524034-50524034
27 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*502G>A SNV Uncertain significance 215130 rs780314255 GRCh37: 22:50962306-50962306
GRCh38: 22:50523877-50523877
28 NCAPH2 , SCO2 NM_005138.3(SCO2):c.512G>A (p.Arg171Gln) SNV Uncertain significance 1029942 GRCh37: 22:50962329-50962329
GRCh38: 22:50523900-50523900
29 NCAPH2 , SCO2 NM_005138.3(SCO2):c.541G>A (p.Val181Ile) SNV Uncertain significance 902939 GRCh37: 22:50962300-50962300
GRCh38: 22:50523871-50523871
30 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*696C>T SNV Uncertain significance 50905 rs145100473 GRCh37: 22:50962500-50962500
GRCh38: 22:50524071-50524071
31 NCAPH2 , SCO2 NM_005138.3(SCO2):c.406A>C (p.Ile136Leu) SNV Uncertain significance 930878 GRCh37: 22:50962435-50962435
GRCh38: 22:50524006-50524006
32 TYMP , NCAPH2 , SCO2 NM_005138.3(SCO2):c.237G>A (p.Arg79=) SNV Uncertain significance 342126 rs150485659 GRCh37: 22:50962604-50962604
GRCh38: 22:50524175-50524175
33 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*299C>T SNV Uncertain significance 382126 rs200605042 GRCh37: 22:50962103-50962103
GRCh38: 22:50523674-50523674
34 TYMP , NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*261G>A SNV Likely benign 139088 rs8139305 GRCh37: 22:50962065-50962065
GRCh38: 22:50523636-50523636
35 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*274G>T SNV Likely benign 139087 rs112793292 GRCh37: 22:50962078-50962078
GRCh38: 22:50523649-50523649
36 NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*836G>A SNV Likely benign 139083 rs61748568 GRCh37: 22:50962640-50962640
GRCh38: 22:50524211-50524211
37 NCAPH2 , SCO2 NM_005138.3(SCO2):c.576C>T (p.Thr192=) SNV Likely benign 702033 rs201909075 GRCh37: 22:50962265-50962265
GRCh38: 22:50523836-50523836
38 SCO2 NM_005138.2(SCO2):c.-142G>C SNV Benign 342134 rs145052206 GRCh37: 22:50964029-50964029
GRCh38: 22:50525600-50525600
39 TYMP , NCAPH2 , SCO2 NM_005138.3(SCO2):c.633A>C (p.Ala211=) SNV Benign 139086 rs12148 GRCh37: 22:50962208-50962208
GRCh38: 22:50523779-50523779
40 TYMP , NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*455G>A SNV Benign 139085 rs131811 GRCh37: 22:50962259-50962259
GRCh38: 22:50523830-50523830
41 TYMP , NCAPH2 , SCO2 NM_005138.3(SCO2):c.59G>C (p.Arg20Pro) SNV Benign 139082 rs140523 GRCh37: 22:50962782-50962782
GRCh38: 22:50524353-50524353
42 TYMP , SCO2 NM_005138.3(SCO2):c.-18G>A SNV Benign 139081 rs74479613 GRCh37: 22:50963905-50963905
GRCh38: 22:50525476-50525476
43 TYMP , NCAPH2 , SCO2 NM_152299.4(NCAPH2):c.*710G>A SNV Benign 139084 rs75485962 GRCh37: 22:50962514-50962514
GRCh38: 22:50524085-50524085
44 SCO2 , TYMP NM_001953.5(TYMP):c.1284T>A (p.Gly428=) SNV Benign 137876 rs1138404 GRCh37: 22:50964446-50964446
GRCh38: 22:50526017-50526017
45 TYMP , SCO2 NM_005138.3(SCO2):c.-78G>C SNV Benign 342130 rs131806 GRCh37: 22:50963965-50963965
GRCh38: 22:50525536-50525536

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex Iv Deficiency, Nuclear Type 2:

72
# Symbol AA change Variation ID SNP ID
1 SCO2 p.Glu140Lys VAR_008874 rs74315511
2 SCO2 p.Ser225Phe VAR_008875 rs80358232
3 SCO2 p.Arg171Trp VAR_013238 rs28937598
4 SCO2 p.Cys133Tyr VAR_070054 rs28937868
5 SCO2 p.Gly193Ser VAR_076281 rs759452074

Expression for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Search GEO for disease gene expression data for Mitochondrial Complex Iv Deficiency, Nuclear Type 2.

Pathways for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

GO Terms for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

Cellular components related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 8.62 SDHB SCO2

Biological processes related to Mitochondrial Complex Iv Deficiency, Nuclear Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 respiratory electron transport chain GO:0022904 8.62 SDHB SCO2

Sources for Mitochondrial Complex Iv Deficiency, Nuclear Type 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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