COXPD6
MCID: CMB017
MIFTS: 38

Combined Oxidative Phosphorylation Deficiency 6 (COXPD6)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 6

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 6:

Name: Combined Oxidative Phosphorylation Deficiency 6 56 12 73 29 13 6 15 71
Coxpd6 56 12 73
Mitochondrial Encephalomyopathy Due to Combined Oxidative Phosphorylation Defect 6 12 58
Severe X-Linked Mitochondrial Encephalomyopathy 12 58
Mitochondrial Encephalomyopathy Due to Coxpd6 12 58
Oxidative Phosphorylation Deficiency, Combined, Type 6 39
Encephalomyopathy, Mitochondrial, X-Linked 56
Encephalomyopathy Mitochondrial X-Linked 73

Characteristics:

Orphanet epidemiological data:

58
severe x-linked mitochondrial encephalomyopathy
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: early childhood;

OMIM:

56
Miscellaneous:
progressive disorder
onset in first year of life
two patients from 1 italian family have been reported (as of april 2010)

Inheritance:
x-linked recessive


HPO:

31
combined oxidative phosphorylation deficiency 6:
Onset and clinical course infantile onset progressive
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 6

OMIM : 56 Combined oxidative phosphorylation deficiency-6 (COXPD6) is an X-linked recessive severe encephalomyopathic disorder with onset in utero or in infancy. Affected patients have hypotonia and severely impaired psychomotor development associated with variably decreased enzymatic activity of mitochondrial respiratory complexes in skeletal muscle or fibroblasts. More variable features may include sensorimotor neuropathy, seizures, severe muscle weakness, abnormal signals in the basal ganglia, hypertrophic cardiomyopathy, deafness, swallowing difficulties, and respiratory insufficiency. Death in childhood may occur (summary by Berger et al., 2011). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (300816)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 6, also known as coxpd6, is related to spondyloepimetaphyseal dysplasia, x-linked and spondyloepimetaphyseal dysplasia, x-linked, with hypomyelinating leukodystrophy, and has symptoms including seizures, muscle weakness and involuntary movements. An important gene associated with Combined Oxidative Phosphorylation Deficiency 6 is AIFM1 (Apoptosis Inducing Factor Mitochondria Associated 1), and among its related pathways/superpathways is Mannose type O-glycan biosynthesis. Affiliated tissues include skeletal muscle, brain and tongue, and related phenotypes are delayed speech and language development and generalized muscle weakness

Disease Ontology : 12 A combined oxidative phosphorylation deficiency that has material basis in hemizygous mutation in AIFM1 on chromosome Xq26.1.

UniProtKB/Swiss-Prot : 73 Combined oxidative phosphorylation deficiency 6: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 6

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency 6:



Diseases related to Combined Oxidative Phosphorylation Deficiency 6

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 6

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 6:

58 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
2 generalized muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003324
3 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
4 areflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001284
5 severe muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0006829
6 moderate global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011343
7 generalized hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001290
8 increased variability in muscle fiber diameter 58 31 hallmark (90%) Very frequent (99-80%) HP:0003557
9 abnormal corpus striatum morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0010994
10 sensory axonal neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003390
11 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
12 irritability 58 31 frequent (33%) Frequent (79-30%) HP:0000737
13 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
14 increased serum lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002151
15 increased csf lactate 58 31 frequent (33%) Frequent (79-30%) HP:0002490
16 increased serum pyruvate 58 31 frequent (33%) Frequent (79-30%) HP:0003542
17 respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0002098
18 hypokinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002375
19 increased connective tissue 58 31 frequent (33%) Frequent (79-30%) HP:0009025
20 tongue fasciculations 58 31 frequent (33%) Frequent (79-30%) HP:0001308
21 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
22 global developmental delay 31 HP:0001263
23 respiratory insufficiency due to muscle weakness 31 HP:0002747
24 peripheral neuropathy 58 Very frequent (99-80%)
25 ragged-red muscle fibers 31 HP:0003200
26 involuntary movements 58 Frequent (79-30%)
27 fasciculations 31 HP:0002380
28 hyporeflexia 31 HP:0001265
29 polyneuropathy 31 HP:0001271
30 tetraplegia 31 HP:0002445
31 central hypotonia 31 HP:0011398
32 abnormality of the basal ganglia 31 HP:0002134
33 psychomotor retardation 31 HP:0025356
34 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
involuntary movements
fasciculations
tetraplegia
hypotonia
more
Respiratory:
respiratory insufficiency due to muscle weakness

Laboratory Abnormalities:
increased lactate in serum and csf
increased pyruvate in serum and csf

Muscle Soft Tissue:
muscle weakness
muscle atrophy
mitochondrial dna depletion (20 to 35% of normal) seen on skeletal muscle biopsy
decreased activity of multiple mitochondrial respiratory complex enzymes
ragged-red fibers
more
Neurologic Peripheral Nervous System:
sensory and motor axonal polyneuropathy

Clinical features from OMIM:

300816

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 6:


seizures, muscle weakness, involuntary movements, muscular fasciculation

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 6

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 6

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 6

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 6:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 6 29 AIFM1

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 6

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 6:

40
Skeletal Muscle, Brain, Tongue

Publications for Combined Oxidative Phosphorylation Deficiency 6

Articles related to Combined Oxidative Phosphorylation Deficiency 6:

# Title Authors PMID Year
1
A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease. 6 56
26173962 2016
2
From ventriculomegaly to severe muscular atrophy: expansion of the clinical spectrum related to mutations in AIFM1. 56 6
25583628 2015
3
Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing. 56 6
22019070 2011
4
Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. 6 56
20362274 2010
5
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 61
27102849 2017

Variations for Combined Oxidative Phosphorylation Deficiency 6

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 6:

6 (show all 34) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AIFM1 NM_004208.4(AIFM1):c.923G>A (p.Gly308Glu)SNV Pathogenic 732658 X:129272612-129272612 X:130138637-130138637
2 AIFM1 NM_004208.4(AIFM1):c.1013G>A (p.Gly338Glu)SNV Pathogenic 732668 X:129271115-129271115 X:130137140-130137140
3 AIFM1 NM_004208.4(AIFM1):c.727G>T (p.Val243Leu)SNV Pathogenic 732675 X:129274562-129274562 X:130140587-130140587
4 AIFM1 NM_004208.4(AIFM1):c.603_605del (p.Arg201del)deletion Pathogenic 11546 rs387906500 X:129281468-129281470 X:130147493-130147495
5 AIFM1 NM_004208.4(AIFM1):c.1436A>G (p.Gln479Arg)SNV Pathogenic 369972 rs1057516211 X:129267300-129267300 X:130133325-130133325
6 AIFM1 NM_004208.4(AIFM1):c.1047C>T (p.Ser349=)SNV Conflicting interpretations of pathogenicity 214080 rs781350745 X:129271081-129271081 X:130137106-130137106
7 AIFM1 NM_004208.4(AIFM1):c.452G>A (p.Arg151Gln)SNV Conflicting interpretations of pathogenicity 214082 rs752742151 X:129281749-129281749 X:130147774-130147774
8 AIFM1 NM_004208.4(AIFM1):c.340G>A (p.Ala114Thr)SNV Conflicting interpretations of pathogenicity 857026 X:129283453-129283453 X:130149478-130149478
9 AIFM1 NM_004208.4(AIFM1):c.1355T>C (p.Val452Ala)SNV Uncertain significance 912874 X:129267381-129267381 X:130133406-130133406
10 AIFM1 NM_004208.4(AIFM1):c.170C>G (p.Ser57Cys)SNV Uncertain significance 445310 rs201711375 X:129290514-129290514 X:130156540-130156540
11 AIFM1 NM_004208.4(AIFM1):c.248A>G (p.Tyr83Cys)SNV Uncertain significance 914370 X:129290436-129290436 X:130156462-130156462
12 AIFM1 NM_004208.4(AIFM1):c.-90G>CSNV Uncertain significance 914371 X:129299720-129299720 X:130165746-130165746
13 AIFM1 NM_004208.4(AIFM1):c.858+13T>GSNV Uncertain significance 913253 X:129273757-129273757 X:130139782-130139782
14 AIFM1 NM_004208.4(AIFM1):c.697-4C>TSNV Uncertain significance 913254 X:129274596-129274596 X:130140621-130140621
15 AIFM1 NM_004208.4(AIFM1):c.-185G>ASNV Uncertain significance 367897 rs770317876 X:129299815-129299815 X:130165841-130165841
16 AIFM1 NM_004208.4(AIFM1):c.*49C>TSNV Uncertain significance 367888 rs1057515766 X:129263483-129263483 X:130129508-130129508
17 AIFM1 NM_004208.4(AIFM1):c.-140C>GSNV Uncertain significance 367895 rs770737305 X:129299770-129299770 X:130165796-130165796
18 AIFM1 NM_004208.4(AIFM1):c.1647A>G (p.Ala549=)SNV Uncertain significance 367889 rs1057515767 X:129264068-129264068 X:130130093-130130093
19 AIFM1 NM_004208.4(AIFM1):c.1644G>A (p.Pro548=)SNV Benign/Likely benign 377456 rs150821143 X:129264071-129264071 X:130130096-130130096
20 AIFM1 NM_004208.4(AIFM1):c.366A>G (p.Glu122=)SNV Benign/Likely benign 367891 rs756883753 X:129281835-129281835 X:130147860-130147860
21 AIFM1 NM_004208.4(AIFM1):c.72C>T (p.Cys24=)SNV Benign/Likely benign 367894 rs373609902 X:129299559-129299559 X:130165585-130165585
22 AIFM1 NM_004208.4(AIFM1):c.1329C>T (p.Tyr443=)SNV Benign/Likely benign 136323 rs143792929 X:129267407-129267407 X:130133432-130133432
23 AIFM1 NM_004208.4(AIFM1):c.1416T>C (p.Ala472=)SNV Benign 136324 rs141324245 X:129267320-129267320 X:130133345-130133345
24 AIFM1 NM_004208.4(AIFM1):c.1833T>C (p.His611=)SNV Benign 136325 rs73556209 X:129263541-129263541 X:130129566-130129566
25 AIFM1 NM_004208.4(AIFM1):c.103C>T (p.Pro35Ser)SNV Benign 136326 rs61730896 X:129299528-129299528 X:130165554-130165554
26 AIFM1 NM_004208.4(AIFM1):c.918C>T (p.Ile306=)SNV Benign 136320 rs12014115 X:129272617-129272617 X:130138642-130138642
27 AIFM1 NM_004208.4(AIFM1):c.996A>G (p.Gln332=)SNV Benign 136322 rs12007545 X:129271132-129271132 X:130137157-130137157
28 AIFM1 NM_004208.4(AIFM1):c.968-14T>ASNV Benign 912875 X:129271174-129271174 X:130137199-130137199
29 AIFM1 NM_004208.4(AIFM1):c.1227T>G (p.Thr409=)SNV Benign 543932 rs61730898 X:129270098-129270098 X:130136123-130136123
30 AIFM1 NM_004208.4(AIFM1):c.597A>G (p.Lys199=)SNV Benign 913255 X:129281476-129281476 X:130147501-130147501
31 AIFM1 NM_004208.4(AIFM1):c.606-15C>TSNV Benign 367890 rs191297808 X:129279559-129279559 X:130145584-130145584
32 AIFM1 NM_004208.4(AIFM1):c.273T>C (p.Asp91=)SNV Benign 367892 rs1139851 X:129283520-129283520 X:130149545-130149545
33 AIFM1 NM_004208.4(AIFM1):c.-165G>ASNV Benign 367896 rs759015293 X:129299795-129299795 X:130165821-130165821
34 AIFM1 NM_004208.4(AIFM1):c.262A>G (p.Met88Val)SNV Benign 367893 rs750098055 X:129283531-129283531 X:130149556-130149556

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 6:

73
# Symbol AA change Variation ID SNP ID
1 AIFM1 p.Gly308Glu VAR_067334
2 AIFM1 p.Gly338Glu VAR_083068

Expression for Combined Oxidative Phosphorylation Deficiency 6

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 6.

Pathways for Combined Oxidative Phosphorylation Deficiency 6

Pathways related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.98 RXYLT1 B3GALNT2

GO Terms for Combined Oxidative Phosphorylation Deficiency 6

Cellular components related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.55 TMEM126A TMEM11 PRODH LONP1 AIFM1
2 Golgi membrane GO:0000139 9.26 RXYLT1 RAB33A HS6ST2 B3GALNT2
3 mitochondrial inner membrane GO:0005743 8.92 TMEM126A TMEM11 PRODH AIFM1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell death GO:0010942 8.62 PRODH AIFM1

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 FAD binding GO:0071949 8.62 PRODH AIFM1

Sources for Combined Oxidative Phosphorylation Deficiency 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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