MCID: ETH011
MIFTS: 51

Ethylmalonic Encephalopathy

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Eye diseases

Aliases & Classifications for Ethylmalonic Encephalopathy

MalaCards integrated aliases for Ethylmalonic Encephalopathy:

Name: Ethylmalonic Encephalopathy 54 12 23 50 24 25 56 71 29 13 42 14 69
Encephalopathy, Petechiae, and Ethylmalonic Aciduria 50 25
Encephalopathy, Ethylmalonic 50 52
Epema Syndrome 50 25
Eye Diseases 52 41
Syndrome of Encephalopathy, Petechiae, and Ethylmalonic Aciduria 50
Abnormality of the Eye 29
Ethe1 Deficiency 23
Disorder of Eye 69
Eme 50
Ee 71

Characteristics:

Orphanet epidemiological data:

56
ethylmalonic encephalopathy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in first months of life
patients are often of mediterranean origin
death usually occurs in first decade of life


HPO:

32
ethylmalonic encephalopathy:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Ethylmalonic Encephalopathy

MedlinePlus : 41 some eye problems are minor and don't last long. but some can lead to a permanent loss of vision. common eye problems include refractive errors cataracts - clouded lenses optic nerve disorders, including glaucoma retinal disorders - problems with the nerve layer at the back of the eye macular degeneration - a disease that destroys sharp, central vision diabetic eye problems conjunctivitis - an infection also known as pinkeye your best defense is to have regular checkups, because eye diseases do not always have symptoms. early detection and treatment could prevent vision loss. see an eye care professional right away if you have a sudden change in vision, if everything looks dim, or if you see flashes of light. other symptoms that need quick attention are pain, double vision, fluid coming from the eye, and inflammation. nih: national eye institute

MalaCards based summary : Ethylmalonic Encephalopathy, also known as encephalopathy, petechiae, and ethylmalonic aciduria, is related to astigmatism and fish-eye disease, and has symptoms including failure to thrive, ataxia and seizures. An important gene associated with Ethylmalonic Encephalopathy is ETHE1 (ETHE1, Persulfide Dioxygenase). Affiliated tissues include eye, skin and brain, and related phenotypes are homeostasis/metabolism and cardiovascular system

NIH Rare Diseases : 50 ethylmalonic encephalopathy is an inherited disorder that is usually evident at birth and affects several body systems, particularly the nervous system. neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. the body's network of blood vessels is also affected. children with this disorder may experience rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). chronic diarrhea is another common feature. ethylmalonic encephalopathy is inherited in an autosomal recessive pattern and caused by mutations in the ethe1 gene. last updated: 8/26/2011

UniProtKB/Swiss-Prot : 71 Ethylmalonic encephalopathy: Autosomal recessive disorder characterized by neurodevelopmental delay and regression, recurrent petechiae, acrocyanosis, diarrhea, leading to death in the first decade of life. It is also associated with persistent lactic acidemia and ethylmalonic and methylsuccinic aciduria.

Genetics Home Reference : 25 Ethylmalonic encephalopathy is an inherited disorder that affects several body systems, particularly the nervous system. Neurological signs and symptoms include delayed development and the loss of previously acquired skills (developmental regression), weak muscle tone (hypotonia), seizures, and abnormal movements. The body's network of blood vessels (the vascular system) is also affected. Children with this disorder often develop rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy.

OMIM : 54
Ethylmalonic encephalopathy is an autosomal recessive severe metabolic disorder of infancy affecting the brain, gastrointestinal tract, and peripheral vessels. The disorder is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Brain MRI shows necrotic lesions in deep gray matter structures. Death usually occurs in the first decade of life (summary by Drousiotou et al., 2011). (602473)

Disease Ontology : 12 A mitochondrial metabolism disease that is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea; it has material basis in homozygous or compound heterozygous mutation in the ETHE1 gene, which encodes a mitochondrial matrix protein, on chromosome 19q13.

Wikipedia : 72 Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. Patients... more...

GeneReviews: NBK453432

Related Diseases for Ethylmalonic Encephalopathy

Diseases related to Ethylmalonic Encephalopathy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 123)
id Related Disease Score Top Affiliating Genes
1 astigmatism 29.5 NDP OPTN
2 fish-eye disease 12.2
3 aland island eye disease 12.2
4 eye disease 12.2
5 bornholm eye disease 12.0
6 eosinophilia-myalgia syndrome 11.9
7 erythema multiforme 11.7
8 norum disease 11.2
9 early myoclonic encephalopathy 11.1
10 erythromelalgia 11.0
11 colobomatous microphthalmia 10.8
12 coccidioidomycosis 10.8
13 superior limbic keratoconjunctivitis 10.8
14 epileptic encephalopathy, early infantile, 4 10.8
15 epileptic encephalopathy, early infantile, 3 10.8
16 night blindness 10.7
17 familial lcat deficiency 10.7
18 cavitary optic disc anomalies 10.7
19 myopia, x-linked 10.7
20 encephalopathy 10.7
21 ocular hypertension 10.6
22 macular dystrophy, vitelliform, 5 10.6 IMPG2 RDH12
23 thyroiditis 10.4
24 macular degeneration, age-related, 1 10.4
25 retinal disease 10.4
26 senior-loken syndrome-1 10.4
27 usher syndrome 10.4
28 aicardi syndrome 10.4
29 coach syndrome 10.4
30 eec syndrome 10.4
31 miller syndrome 10.4
32 waardenburg syndrome, type 4b 10.4
33 cat eye syndrome 10.4
34 waardenburg syndrome, type 4c 10.4
35 waardenburg syndrome, type 2e, with or without neurologic involvement 10.4
36 pulmonary venoocclusive disease 10.4 ABCC6 IMPG2 RDH12
37 senior-loken syndrome 5 10.3
38 meesmann corneal dystrophy 10.3
39 retinoschisis 10.3
40 ptosis 10.3
41 loiasis 10.3
42 glaucoma, normal tension 10.3
43 stickler sydrome, type i, nonsyndromic ocular 10.3
44 pigment dispersion syndrome 10.3
45 optic nerve disease 10.3
46 exophthalmos 10.3
47 senior-loken syndrome 8 10.3
48 senior-loken syndrome 6 10.3
49 microphthalmia 10.3
50 rhinosporidiosis 10.3

Graphical network of the top 20 diseases related to Ethylmalonic Encephalopathy:



Diseases related to Ethylmalonic Encephalopathy

Symptoms & Phenotypes for Ethylmalonic Encephalopathy

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Skin Nails & Hair- Skin:
petechiae
orthostatic acrocyanosis

Abdomen- Gastroin testinal:
chronic diarrhea

Cardiovascular- Vascular:
orthostatic acrocyanosis

Neurologic- Central Nervous System:
hypotonia
mental retardation
ataxia
developmental delay
seizures
more
Laboratory- Abnormalities:
lactic acidemia
ethylmalonic aciduria
methylsuccinic aciduria
cytochrome c oxidase deficiency in skeletal muscle and brain
increased serum c4 and c5 acylcarnitine esters
more
Head And Neck- Eyes:
retinal lesions with tortuous vessels


Clinical features from OMIM:

602473

Human phenotypes related to Ethylmalonic Encephalopathy:

32 (show all 16)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 ataxia 32 HP:0001251
3 seizures 32 HP:0001250
4 encephalopathy 32 HP:0001298
5 global developmental delay 32 HP:0001263
6 lactic acidosis 32 HP:0003128
7 intellectual disability 32 HP:0001249
8 petechiae 32 HP:0000967
9 muscular hypotonia 32 HP:0001252
10 developmental regression 32 HP:0002376
11 chronic diarrhea 32 HP:0002028
12 ethylmalonic aciduria 32 HP:0003219
13 abnormality of the retinal vasculature 32 HP:0008046
14 abnormality of extrapyramidal motor function 32 HP:0002071
15 cytochrome c oxidase-negative muscle fibers 32 HP:0003688
16 focal t2 hyperintense basal ganglia lesion 32 HP:0007183

UMLS symptoms related to Ethylmalonic Encephalopathy:


eye manifestations, pain in or around eye, redness or discharge of eye, pathological conditions, signs and symptoms, lid retraction, visual disturbance, ataxia, seizures, abnormality of extrapyramidal motor function

MGI Mouse Phenotypes related to Ethylmalonic Encephalopathy:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.9 ABCA4 ABCC6 ACADS CHM ETHE1 LCAT
2 cardiovascular system MP:0005385 9.86 ABCA4 ABCC6 CHM LCAT NDP PAX6
3 pigmentation MP:0001186 9.43 SERPINF1 SLC31A1 ABCA4 CHM NDP PAX6
4 vision/eye MP:0005391 9.28 ABCA4 ABCC6 CHM LCAT NDP PAX6

Drugs & Therapeutics for Ethylmalonic Encephalopathy

Search Clinical Trials , NIH Clinical Center for Ethylmalonic Encephalopathy

Inferred drug relations via UMLS 69 / NDF-RT 48 :


Cochrane evidence based reviews: ethylmalonic encephalopathy

Genetic Tests for Ethylmalonic Encephalopathy

Genetic tests related to Ethylmalonic Encephalopathy:

id Genetic test Affiliating Genes
1 Ethylmalonic Encephalopathy 29 24 ETHE1
2 Abnormality of the Eye 29

Anatomical Context for Ethylmalonic Encephalopathy

MalaCards organs/tissues related to Ethylmalonic Encephalopathy:

39
Eye, Skin, Brain, Skeletal Muscle, Liver

Publications for Ethylmalonic Encephalopathy

Articles related to Ethylmalonic Encephalopathy:

(show all 40)
id Title Authors Year
1
Neurological and Vascular Manifestations of Ethylmalonic Encephalopathy. ( 28698729 )
2017
2
Bioenergetics dysfunction, mitochondrial permeability transition pore opening and lipid peroxidation induced by hydrogen sulfide as relevant pathomechanisms underlying the neurological dysfunction characteristic of ethylmalonic encephalopathy. ( 28624490 )
2017
3
Ethylmalonic Encephalopathy in an Indian Boy. ( 27771676 )
2016
4
Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease. ( 26917598 )
2016
5
Diffusion restriction in ethylmalonic encephalopathy - An imaging evidence of the pathophysiology of the disease. ( 26992475 )
2016
6
Successful treatment of a patient with ethylmalonic encephalopathy by intravenous N-acetylcysteine. ( 27830356 )
2016
7
Protein polysulfidation-dependent persulfide dioxygenase activity of ethylmalonic encephalopathy protein 1. ( 27742479 )
2016
8
Severe early onset ethylmalonic encephalopathy with West syndrome. ( 26194623 )
2015
9
Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy. ( 25596185 )
2015
10
The mitochondrial sulfur dioxygenase ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 is required for amino acid catabolism during carbohydrate starvation and embryo development in Arabidopsis. ( 24692429 )
2014
11
Ethylmalonic encephalopathy ETHE1 R163W/R163Q mutations alter protein stability and redox properties of the iron centre. ( 25198162 )
2014
12
Altered sulfide (H(2)S) metabolism in ethylmalonic encephalopathy. ( 23284046 )
2013
13
An infant with ethylmalonic encephalopathy masquerading as a hematologic disorder. ( 22805253 )
2013
14
Morphologic evidence of diffuse vascular damage in human and in the experimental model of ethylmalonic encephalopathy. ( 22020834 )
2012
15
Effective AAV-mediated gene therapy in a mouse model of ethylmalonic encephalopathy. ( 22903887 )
2012
16
Ethylmalonic encephalopathy associated with crescentic glomerulonephritis. ( 22584649 )
2012
17
Ethylmalonic encephalopathy: application of improved biochemical and molecular diagnostic approaches. ( 20528888 )
2011
18
Chronic exposure to sulfide causes accelerated degradation of cytochrome c oxidase in ethylmalonic encephalopathy. ( 20812865 )
2011
19
Proteomics reveals that redox regulation is disrupted in patients with ethylmalonic encephalopathy. ( 21410200 )
2011
20
Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy. ( 20657580 )
2010
21
Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy. ( 20978941 )
2010
22
Novel ETHE1 mutation in a carrier couple having prior offspring affected with ethylmalonic encephalopathy: Genetic analysis, clinical management and reproductive outcome. ( 21472225 )
2010
23
Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. ( 19136963 )
2009
24
Ethylmalonic encephalopathy. Another patient from Kuwait. ( 21048580 )
2009
25
Clinical heterogeneity in ethylmalonic encephalopathy. ( 19289697 )
2009
26
Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy. ( 18593870 )
2008
27
Ethylmalonic encephalopathy: clinical and biochemical observations. ( 17712735 )
2007
28
Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as marker of SCAD defect and ethylmalonic encephalopathy. ( 16906473 )
2006
29
ETHE1 mutations are specific to ethylmalonic encephalopathy. ( 16183799 )
2006
30
A case of ethylmalonic encephalopathy with atypical clinical and biochemical presentation. ( 16828325 )
2006
31
Ethylmalonic encephalopathy-report of two cases. ( 16376514 )
2006
32
Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. ( 14732903 )
2004
33
Brain mitochondrial impairment in ethylmalonic encephalopathy. ( 15311356 )
2004
34
The role of methionine in ethylmalonic encephalopathy with petechiae. ( 15096407 )
2004
35
Mutation analysis of copper transporter genes in patients with ethylmalonic encephalopathy, mitochondriopathies and copper deficiency phenotypes. ( 12872841 )
2003
36
Ethylmalonic encephalopathy: further clinical and neuroradiological characterization. ( 12382164 )
2002
37
Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin. ( 11916321 )
2001
38
Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise from abnormal isoleucine metabolism. ( 9667231 )
1998
39
Central nervous system malformations in ethylmalonic encephalopathy. ( 9475600 )
1998
40
Ethylmalonic Encephalopathy ( 28933811 )
1993

Variations for Ethylmalonic Encephalopathy

UniProtKB/Swiss-Prot genetic disease variations for Ethylmalonic Encephalopathy:

71
id Symbol AA change Variation ID SNP ID
1 ETHE1 p.Tyr38Cys VAR_023395
2 ETHE1 p.Thr136Ala VAR_023396
3 ETHE1 p.Arg163Trp VAR_023397 rs28940289
4 ETHE1 p.Leu185Arg VAR_023398 rs387906987
5 ETHE1 p.Leu55Pro VAR_069507 rs182983506
6 ETHE1 p.Thr152Ile VAR_069508
7 ETHE1 p.Arg163Gln VAR_069509 rs745656120
8 ETHE1 p.Thr164Lys VAR_069510
9 ETHE1 p.Asp196Asn VAR_069511 rs763799125

ClinVar genetic disease variations for Ethylmalonic Encephalopathy:

6 (show all 20)
id Gene Variation Type Significance SNP ID Assembly Location
1 RDH12 NM_152443.2(RDH12): c.806_810delCCCTG (p.Ala269Glyfs) deletion Pathogenic rs386834261 GRCh37 Chromosome 14, 68196055: 68196059
2 ETHE1 NM_014297.4(ETHE1): c.487C> T (p.Arg163Trp) single nucleotide variant Pathogenic rs28940289 GRCh37 Chromosome 19, 44015607: 44015607
3 ETHE1 NM_014297.4(ETHE1): c.3G> T (p.Met1Ile) single nucleotide variant Pathogenic rs119103249 GRCh37 Chromosome 19, 44031327: 44031327
4 ETHE1 ETHE1, 1-BP INS, 604G insertion Pathogenic
5 ETHE1 ETHE1, 1-BP INS, 221A insertion Pathogenic
6 ETHE1 ETHE1, 11-BP DEL, NT440 deletion Pathogenic
7 ETHE1 ETHE1, IVS4DS, G-T, +1 single nucleotide variant Pathogenic
8 ETHE1 ETHE1, EX4DEL deletion Pathogenic
9 ABCC6 NM_001171.5(ABCC6): c.3389C> T (p.Thr1130Met) single nucleotide variant Pathogenic/Likely pathogenic rs63750459 GRCh37 Chromosome 16, 16256967: 16256967
10 ETHE1 NM_014297.4(ETHE1): c.554T> G (p.Leu185Arg) single nucleotide variant Pathogenic rs387906987 GRCh37 Chromosome 19, 44012968: 44012968
11 VPS13B NM_017890.4(VPS13B): c.2591C> A (p.Ser864Ter) single nucleotide variant Pathogenic/Likely pathogenic rs140936527 GRCh37 Chromosome 8, 100286501: 100286501
12 ETHE1 NM_014297.4(ETHE1): c.488G> A (p.Arg163Gln) single nucleotide variant Likely pathogenic rs745656120 GRCh38 Chromosome 19, 43511454: 43511454
13 CNGA3 NM_001298.2(CNGA3): c.1688G> A (p.Arg563His) single nucleotide variant Pathogenic/Likely pathogenic rs552069173 GRCh37 Chromosome 2, 99013321: 99013321
14 ETHE1 NC_000019.9: g.(?_44015589)_(44015719_?)del deletion Pathogenic GRCh37 Chromosome 19, 44015589: 44015719
15 CNGB3 NM_019098.4(CNGB3): c.1285delT (p.Ser429Leufs) deletion Pathogenic/Likely pathogenic GRCh37 Chromosome 8, 87645015: 87645015
16 ETHE1 NM_014297.4(ETHE1): c.505+1G> C single nucleotide variant Pathogenic rs935855792 GRCh37 Chromosome 19, 44015588: 44015588
17 ABCC6 NM_001171.5(ABCC6): c.4104delC (p.Asp1368Glufs) deletion Pathogenic rs72664237 GRCh38 Chromosome 16, 16154732: 16154732
18 ETHE1 NM_014297.4(ETHE1): c.494A> G (p.Asp165Gly) single nucleotide variant Likely pathogenic rs756235299 GRCh38 Chromosome 19, 43511448: 43511448
19 ETHE1 NM_014297.4(ETHE1): c.482G> A (p.Cys161Tyr) single nucleotide variant Likely pathogenic GRCh38 Chromosome 19, 43511460: 43511460
20 IMPG2 NM_016247.3(IMPG2): c.1680T> A (p.Tyr560Ter) single nucleotide variant Pathogenic rs758291149 GRCh37 Chromosome 3, 100963495: 100963495

Expression for Ethylmalonic Encephalopathy

Search GEO for disease gene expression data for Ethylmalonic Encephalopathy.

Pathways for Ethylmalonic Encephalopathy

GO Terms for Ethylmalonic Encephalopathy

Biological processes related to Ethylmalonic Encephalopathy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.55 ACADS CHM ETHE1 RDH12 SDHA
2 response to stimulus GO:0050896 9.35 ABCA4 ABCC6 CHM NDP RDH12
3 photoreceptor cell maintenance GO:0045494 9.26 ABCA4 RDH12
4 visual perception GO:0007601 9.17 ABCA4 ABCC6 CHM IMPG2 NDP PAX6

Molecular functions related to Ethylmalonic Encephalopathy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.02 ACADS CHM ETHE1 RDH12 SDHA
2 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 8.96 ACADS SDHA

Sources for Ethylmalonic Encephalopathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
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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