COXPD24
MCID: CMB064
MIFTS: 29

Combined Oxidative Phosphorylation Deficiency 24 (COXPD24)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 24

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 24:

Name: Combined Oxidative Phosphorylation Deficiency 24 57 12 72 29 6 70
Coxpd24 57 12 58 72
Combined Oxidative Phosphorylation Defect Type 24 58 17
Oxidative Phosphorylation Deficiency, Combined, Type 24 39

Characteristics:

Orphanet epidemiological data:

58
combined oxidative phosphorylation defect type 24
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: adolescent,adult;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype and severity
early death may occur
onset in infancy (most patients)


HPO:

31
combined oxidative phosphorylation deficiency 24:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 24

OMIM® : 57 Combined oxidative phosphorylation deficiency-24 (COXPD24) is an autosomal recessive mitochondrial disorder with wide phenotypic variability. Most patients present in infancy with delayed neurodevelopment, refractory seizures, hypotonia, and hearing impairment due to auditory neuropathy. Less common features may include cortical blindness, renal dysfunction, and/or liver involvement, suggestive of Alpers syndrome (MTDPS4A; 203700). Patients with the severe phenotype tend to have brain abnormalities on imaging, including cerebral atrophy and hyperintensities in the basal ganglia and brainstem, consistent with Leigh syndrome. Laboratory values may be normal or show increased lactate and evidence of mitochondrial respiratory chain defects, particularly in muscle. Some patients achieve little developmental milestones and may die in infancy or early childhood. However, some patients have a less severe phenotype manifest only by myopathy (summary by Sofou et al., 2015, Vanlander et al., 2015, and Mizuguchi et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (616239) (Updated 20-May-2021)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 24, also known as coxpd24, is related to mitochondrial dna depletion syndrome 4a, and has symptoms including facial paresis An important gene associated with Combined Oxidative Phosphorylation Deficiency 24 is NARS2 (Asparaginyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include skeletal muscle and brain, and related phenotypes are dysarthria and intellectual disability, mild

Disease Ontology : 12 A combined oxidative phosphorylation deficiency typically characterized by delayed neurodevelopment, refractory seizures, hypotonia, and hearing impairment that has material basis in homozygous or compound heterozygous mutation in NARS2 on chromosome 11q14.1.

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 24: An autosomal recessive mitochondrial disorder with wide phenotypic variability. Some patients have a milder form affecting only skeletal muscle, whereas others may have a more severe disorder, reminiscent of Alpers syndrome. Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 24

Diseases related to Combined Oxidative Phosphorylation Deficiency 24 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 mitochondrial dna depletion syndrome 4a 10.9

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 24

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 24:

31 (show all 34)
# Description HPO Frequency HPO Source Accession
1 dysarthria 31 occasional (7.5%) HP:0001260
2 intellectual disability, mild 31 occasional (7.5%) HP:0001256
3 seizure 31 occasional (7.5%) HP:0001250
4 spasticity 31 HP:0001257
5 agenesis of corpus callosum 31 HP:0001274
6 hyperreflexia 31 HP:0001347
7 ptosis 31 HP:0000508
8 nystagmus 31 HP:0000639
9 facial palsy 31 HP:0010628
10 developmental regression 31 HP:0002376
11 hearing impairment 31 HP:0000365
12 global developmental delay 31 HP:0001263
13 microcephaly 31 HP:0000252
14 optic atrophy 31 HP:0000648
15 myopathy 31 HP:0003198
16 skeletal muscle atrophy 31 HP:0003202
17 elevated serum creatine kinase 31 HP:0003236
18 areflexia 31 HP:0001284
19 increased serum lactate 31 HP:0002151
20 hyporeflexia 31 HP:0001265
21 hypoplasia of the corpus callosum 31 HP:0002079
22 increased csf lactate 31 HP:0002490
23 feeding difficulties 31 HP:0011968
24 cerebellar atrophy 31 HP:0001272
25 status epilepticus 31 HP:0002133
26 generalized hypotonia 31 HP:0001290
27 proximal muscle weakness 31 HP:0003701
28 cerebral visual impairment 31 HP:0100704
29 neuronal loss in central nervous system 31 HP:0002529
30 cns hypomyelination 31 HP:0003429
31 gliosis 31 HP:0002171
32 focal segmental glomerulosclerosis 31 HP:0000097
33 metabolic alkalosis 31 HP:0200114
34 neurodegeneration 31 HP:0002180

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
developmental regression
global developmental delay
status epilepticus
more
Muscle Soft Tissue:
muscle weakness
myopathy
hypotonia
muscle atrophy
combined oxidative phosphorylation deficiency, complexes i, iii, and iv
more
Head And Neck Head:
microcephaly

Abdomen Gastrointestinal:
feeding difficulties

Abdomen Liver:
fatty changes (in some patients)

Laboratory Abnormalities:
increased serum lactate, variable
increased csf lactate, variable
increased urinary excretion of citric acid metabolites, variable

Head And Neck Eyes:
ptosis
nystagmus
optic atrophy
cortical blindness

Head And Neck Ears:
hearing impairment
deafness
auditory neuropathy

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia

Head And Neck Face:
facial muscle weakness

Genitourinary Kidneys:
tubulopathy (in some patients)
focal segmental glomerulosclerosis (in some patients)

Clinical features from OMIM®:

616239 (Updated 20-May-2021)

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 24:


facial paresis

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 24

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 24

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 24

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 24:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 24 29 NARS2

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 24

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 24:

40
Skeletal Muscle, Brain

Publications for Combined Oxidative Phosphorylation Deficiency 24

Articles related to Combined Oxidative Phosphorylation Deficiency 24:

# Title Authors PMID Year
1
Lethal NARS2-Related Disorder Associated With Rapidly Progressive Intractable Epilepsy and Global Brain Atrophy. 6 57
30327238 2018
2
PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder. 57 6
28077841 2017
3
Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome. 6 57
25807530 2015
4
Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2). 57 6
25385316 2015
5
Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. 6 57
25629079 2015
6
Phenotypic and genotypic variability in Alpers syndrome. 6 57
22237560 2012
7
Management of NARS2-Related Mitochondrial Disorder is Complex. 57
30583950 2019
8
Reply to Finsterer Regarding Lethal NARS2-Related Disorder Associated With Rapidly Progressive Intractable Epilepsy and Global Brain Atrophy. 57
30686630 2019

Variations for Combined Oxidative Phosphorylation Deficiency 24

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 24:

6 (show all 22)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NARS2 NM_024678.6(NARS2):c.822G>C (p.Gln274His) SNV Pathogenic 183150 rs730882154 GRCh37: 11:78204109-78204109
GRCh38: 11:78493063-78493063
2 NARS2 NM_024678.6(NARS2):c.641C>T (p.Pro214Leu) SNV Pathogenic 183151 rs730882155 GRCh37: 11:78239936-78239936
GRCh38: 11:78528890-78528890
3 NARS2 NM_024678.6(NARS2):c.594+1G>A SNV Pathogenic 632573 rs1035101172 GRCh37: 11:78270584-78270584
GRCh38: 11:78559538-78559538
4 NARS2 NM_024678.6(NARS2):c.707T>G (p.Phe236Cys) SNV Pathogenic 632577 rs1565235204 GRCh37: 11:78204224-78204224
GRCh38: 11:78493178-78493178
5 NARS2 NM_024678.6(NARS2):c.1184T>G (p.Leu395Arg) SNV Pathogenic 632578 rs763770414 GRCh37: 11:78154785-78154785
GRCh38: 11:78443739-78443739
6 NARS2 NM_024678.6(NARS2):c.151C>T (p.Arg51Cys) SNV Pathogenic 545046 rs367584549 GRCh37: 11:78282480-78282480
GRCh38: 11:78571435-78571435
7 NARS2 NM_024678.6(NARS2):c.167A>G (p.Gln56Arg) SNV Pathogenic 422720 rs201751992 GRCh37: 11:78282464-78282464
GRCh38: 11:78571419-78571419
8 NARS2 NM_024678.6(NARS2):c.631T>A (p.Phe211Ile) SNV Pathogenic 424270 rs755122704 GRCh37: 11:78239946-78239946
GRCh38: 11:78528900-78528900
9 NARS2 NM_024678.6(NARS2):c.1253G>A (p.Arg418His) SNV Likely pathogenic 802711 rs535877562 GRCh37: 11:78154716-78154716
GRCh38: 11:78443670-78443670
10 NARS2 NM_024678.6(NARS2):c.969T>A (p.Tyr323Ter) SNV Likely pathogenic 632571 rs565224393 GRCh37: 11:78180350-78180350
GRCh38: 11:78469304-78469304
11 NARS2 NM_024678.6(NARS2):c.1142A>G (p.Asn381Ser) SNV Likely pathogenic 632572 rs1565216037 GRCh37: 11:78176944-78176944
GRCh38: 11:78465898-78465898
12 NARS2 NM_024678.6(NARS2):c.500A>G (p.His167Arg) SNV Conflicting interpretations of pathogenicity 632580 rs750594551 GRCh37: 11:78277191-78277191
GRCh38: 11:78566145-78566145
13 NARS2 NM_024678.6(NARS2):c.545T>A (p.Ile182Lys) SNV Uncertain significance 872894 GRCh37:
GRCh38:
14 NARS2 NM_024678.6(NARS2):c.1303C>T (p.Arg435Cys) SNV Uncertain significance 1028840 GRCh37: 11:78147847-78147847
GRCh38: 11:78436801-78436801
15 NARS2 NM_024678.6(NARS2):c.606_607insAGC (p.Leu203_Lys204insSer) Insertion Uncertain significance 1028841 GRCh37: 11:78239970-78239971
GRCh38: 11:78528924-78528925
16 NARS2 NM_024678.6(NARS2):c.847A>G (p.Thr283Ala) SNV Uncertain significance 1029917 GRCh37: 11:78189705-78189705
GRCh38: 11:78478659-78478659
17 NARS2 NM_024678.6(NARS2):c.141+5G>C SNV Uncertain significance 1033638 GRCh37: 11:78285388-78285388
GRCh38: 11:78574343-78574343
18 NARS2 NM_024678.6(NARS2):c.436A>G (p.Arg146Gly) SNV Uncertain significance 1033639 GRCh37: 11:78277255-78277255
GRCh38: 11:78566209-78566209
19 NARS2 NM_024678.6(NARS2):c.640C>A (p.Pro214Thr) SNV Uncertain significance 1033640 GRCh37: 11:78239937-78239937
GRCh38: 11:78528891-78528891
20 NARS2 NM_024678.6(NARS2):c.1361A>G (p.Gln454Arg) SNV Uncertain significance 953071 rs1399346230 GRCh37: 11:78147789-78147789
GRCh38: 11:78436743-78436743
21 NARS2 NM_024678.6(NARS2):c.260A>C (p.Asn87Thr) SNV Benign 380000 rs10501429 GRCh37: 11:78279790-78279790
GRCh38: 11:78568744-78568744
22 NARS2 NM_024678.6(NARS2):c.595-6T>G SNV not provided 440990 rs774848576 GRCh37: 11:78239988-78239988
GRCh38: 11:78528942-78528942

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 24:

72
# Symbol AA change Variation ID SNP ID
1 NARS2 p.Pro214Leu VAR_073250 rs730882155
2 NARS2 p.Asn381Ser VAR_073724 rs156521603

Expression for Combined Oxidative Phosphorylation Deficiency 24

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 24.

Pathways for Combined Oxidative Phosphorylation Deficiency 24

GO Terms for Combined Oxidative Phosphorylation Deficiency 24

Sources for Combined Oxidative Phosphorylation Deficiency 24

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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