MCID: CMB026
MIFTS: 27

Combined Oxidative Phosphorylation Deficiency 12

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 12

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 12:

Name: Combined Oxidative Phosphorylation Deficiency 12 54 24 25 71 29 13 69
Coxpd12 25 56 71
Ltbl 25 56 71
Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate 25 71
Leukoencephalopathy-Thalamus and Brainstem Anomalies-High Lactate Syndrome 56
Combined Oxidative Phosphorylation Defect Type 12 56

Characteristics:

Orphanet epidemiological data:

56
leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in first year of life
two main phenotypes, severe and mild
mild cases show clinical, biochemical, and mri improvement after the second year of life


HPO:

32
combined oxidative phosphorylation deficiency 12:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Combined Oxidative Phosphorylation Deficiency 12

OMIM : 54
COXPD12 is an autosomal recessive mitochondrial neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability (summary by Steenweg et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (614924)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 12, also known as coxpd12, is related to metabolic acidosis, and has symptoms including failure to thrive, visual impairment and dystonia. An important gene associated with Combined Oxidative Phosphorylation Deficiency 12 is EARS2 (Glutamyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include thalamus, brain and liver.

Genetics Home Reference : 25 Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a disorder that affects the brain. LTBL is one of a group of genetic disorders called leukodystrophies, which feature abnormalities of the nervous system's white matter. White matter consists of nerve fibers covered by a fatty substance, called myelin, that insulates nerve fibers and promotes the rapid transmission of nerve impulses.

UniProtKB/Swiss-Prot : 71 Combined oxidative phosphorylation deficiency 12: An autosomal recessive, mitochondrial, neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2- weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 12

Diseases related to Combined Oxidative Phosphorylation Deficiency 12 via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 metabolic acidosis 10.1

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 12

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Neurologic- Central Nervous System:
seizures
dysplastic corpus callosum
thinning of the corpus callosum
delayed psychomotor development (in severe cases)
psychomotor regression (in milder cases)
more
Laboratory- Abnormalities:
increased serum lactate
abnormal liver enzymes, intermittent (1 patient)
increased alpha-fetoprotein (1 patient)

Abdomen- Liver:
hepatomegaly (1 patient)
macrovesicular steatosis (1 patient)
cholestasis (1 patient)
fibrosis, mild (1 patient)

Cardiovascular- Heart:
interventricular septal hypertrophy (1 patient)

Head And Neck- Eyes:
visual impairment
ptosis
ophthalmoplegia

Metabolic Features:
lactic acidosis

Muscle Soft Tissue:
hypotonia, neonatal
ragged-red fibers
muscle biopsy shows cytochrome c oxidase-negative fibers
decreased activities of mitochondrial complexes i, iii, and iv
impaired mitochondrial respiration

Head And Neck- Mouth:
cleft palate (1 patient)


Clinical features from OMIM:

614924

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 12:

32 (show all 25)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 visual impairment 32 HP:0000505
3 dystonia 32 HP:0001332
4 absent speech 32 HP:0001344
5 hepatomegaly 32 occasional (7.5%) HP:0002240
6 seizures 32 HP:0001250
7 ptosis 32 HP:0000508
8 cleft palate 32 occasional (7.5%) HP:0000175
9 global developmental delay 32 HP:0001263
10 lactic acidosis 32 HP:0003128
11 increased serum lactate 32 HP:0002151
12 bradykinesia 32 HP:0002067
13 neonatal hypotonia 32 HP:0001319
14 hypoplasia of the corpus callosum 32 HP:0002079
15 dysplastic corpus callosum 32 HP:0006989
16 leukoencephalopathy 32 HP:0002352
17 cholestasis 32 occasional (7.5%) HP:0001396
18 developmental regression 32 HP:0002376
19 ophthalmoplegia 32 HP:0000602
20 spastic tetraparesis 32 HP:0001285
21 ragged-red muscle fibers 32 HP:0003200
22 macrovesicular hepatic steatosis 32 occasional (7.5%) HP:0001403
23 decreased activity of mitochondrial complex i 32 HP:0011923
24 decreased activity of mitochondrial complex iii 32 HP:0011924
25 decreased activity of mitochondrial complex iv 32 HP:0008347

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 12:


ophthalmoplegia, seizures

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 12

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 12

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 12

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 12:

id Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 12 29 24 EARS2

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 12

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 12:

39
Thalamus, Brain, Liver

Publications for Combined Oxidative Phosphorylation Deficiency 12

Variations for Combined Oxidative Phosphorylation Deficiency 12

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 12:

71 (show all 14)
id Symbol AA change Variation ID SNP ID
1 EARS2 p.Arg55His VAR_069235 rs770862902
2 EARS2 p.Lys65Glu VAR_069236 rs397514595
3 EARS2 p.Glu96Lys VAR_069237 rs397514593
4 EARS2 p.Arg107His VAR_069238
5 EARS2 p.Arg108Trp VAR_069239 rs376103091
6 EARS2 p.Gly110Ser VAR_069240 rs201842633
7 EARS2 p.Cys167Tyr VAR_069241 rs397514594
8 EARS2 p.Arg168Gly VAR_069242 rs397514591
9 EARS2 p.Gly204Ser VAR_069243 rs397514592
10 EARS2 p.Gly224Ser VAR_069244 rs141129877
11 EARS2 p.Gly317Cys VAR_069245 rs746838793
12 EARS2 p.Arg516Gln VAR_069247 rs201727231
13 EARS2 p.Arg107Cys VAR_076183
14 EARS2 p.Arg489Gln VAR_076184 rs757965573

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 12:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 EARS2 NM_001083614.1(EARS2): c.322C> T (p.Arg108Trp) single nucleotide variant Pathogenic/Likely pathogenic rs376103091 GRCh37 Chromosome 16, 23555998: 23555998
2 EARS2 NM_001083614.1(EARS2): c.502A> G (p.Arg168Gly) single nucleotide variant Pathogenic rs397514591 GRCh37 Chromosome 16, 23546665: 23546665
3 EARS2 NM_001083614.1(EARS2): c.328G> A (p.Gly110Ser) single nucleotide variant Pathogenic/Likely pathogenic rs201842633 GRCh37 Chromosome 16, 23555992: 23555992
4 EARS2 NM_001083614.1(EARS2): c.610G> A (p.Gly204Ser) single nucleotide variant Pathogenic rs397514592 GRCh37 Chromosome 16, 23546557: 23546557
5 EARS2 NM_001083614.1(EARS2): c.286G> A (p.Glu96Lys) single nucleotide variant Pathogenic rs397514593 GRCh37 Chromosome 16, 23563479: 23563479
6 EARS2 NM_001083614.1(EARS2): c.500G> A (p.Cys167Tyr) single nucleotide variant Pathogenic rs397514594 GRCh37 Chromosome 16, 23546667: 23546667
7 EARS2 NM_001083614.1(EARS2): c.193A> G (p.Lys65Glu) single nucleotide variant Pathogenic rs397514595 GRCh37 Chromosome 16, 23563572: 23563572

Expression for Combined Oxidative Phosphorylation Deficiency 12

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 12.

Pathways for Combined Oxidative Phosphorylation Deficiency 12

GO Terms for Combined Oxidative Phosphorylation Deficiency 12

Sources for Combined Oxidative Phosphorylation Deficiency 12

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
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30 HGMD
31 HMDB
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33 ICD10
34 ICD10 via Orphanet
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37 KEGG
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42 MeSH
43 MESH via Orphanet
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52 Novoseek
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59 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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