MCID: MTC056
MIFTS: 49

Mitochondrial Dna Depletion Syndrome 4a malady

Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Liver diseases categories

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 4a

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Sources:
49OMIM, 10Disease Ontology, 11diseasecard, 67UniProtKB/Swiss-Prot, 45NIH Rare Diseases, 23Genetics Home Reference, 47Novoseek, 12DISEASES, 51Orphanet, 65UMLS, 22GeneTests, 46NINDS, 24GTR, 36MeSH, 42NCIt, 59SNOMED-CT, 66UMLS via Orphanet, 28ICD10 via Orphanet, 37MESH via Orphanet, 34MedGen
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Aliases & Descriptions for Mitochondrial Dna Depletion Syndrome 4a:

Name: Mitochondrial Dna Depletion Syndrome 4a 49 10 11 67
Alpers Syndrome 10 45 23 47 12 51 65 67
Alpers-Huttenlocher Syndrome 10 45 22 23 51 67
Alpers Progressive Infantile Poliodystrophy 10 45 22 23 67
Progressive Sclerosing Poliodystrophy 10 23 46 24
Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis 45 23 67
Diffuse Cerebral Sclerosis of Schilder 23 65 36
Alpers Disease 45 22 23
Neuronal Degeneration of Childhood with Liver Disease, Progressive 45 22
Alpers' Disease 10 46
Pndc 45 67
Neuronal Degeneration of Childhood with Liver Disease Progressive 67
 
Progressive Neuronal Degeneration of Childhood with Liver Disease 51
Mitochondrial Dna Depletion Syndrome 4a Alpers Type 67
Alpers Progressive Sclerosing Poliodystrophy 51
Diffuse Cerebral Degeneration in Infancy 45
Progressive Cerebral Poliodystrophy 45
Poliodystrophia Cerebri Progressiva 45
Gray-Matter Degeneration 10
Infantile Poliodystrophy 45
Alper's Syndrome 10
Mtdps4a 67
Ahs 67


Classifications:



Characteristics (Orphanet epidemiological data):

51
alpers syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy,Neonatal


External Ids:

OMIM49 203700
Disease Ontology10 DOID:1442
NCIt42 C35257
MeSH36 D002549
Orphanet51 726
SNOMED-CT59 20415001
UMLS via Orphanet66 C0205710
ICD10 via Orphanet28 G31.8
MESH via Orphanet37 D002549
MedGen34 C0205710

Summaries for Mitochondrial Dna Depletion Syndrome 4a

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OMIM:49 Mitochondrial DNA depletion syndrome-4A, also known as Alpers syndrome, is an autosomal recessive disorder... (203700) more...

MalaCards based summary: Mitochondrial Dna Depletion Syndrome 4a, also known as alpers syndrome, is related to breast cancer and adrenoleukodystrophy, and has symptoms including microcephaly, abnormality of the eye and seizures. An important gene associated with Mitochondrial Dna Depletion Syndrome 4a is POLG (Polymerase (DNA Directed), Gamma), and among its related pathways are Cell Cycle Control of Chromosomal Replication and Nucleotide Metabolism. Affiliated tissues include liver, cortex and brain.

Disease Ontology:10 A cerebral degeneration that results in progressive degeneration of grey matter in the cerebrum and has symptom convulsions.

Genetics Home Reference:23 Alpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.

NIH Rare Diseases:45 Alpers syndrome is a progressive neurologic disorder that begins during childhood and is complicated in many instances by serious liver disease. symptoms include increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia).   most often alpers syndrome is caused by mutations in the polg gene. last updated: 1/24/2011

NINDS:46 Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical symptoms: psychomotor regression (dementia); seizures; and liver disease.

UniProtKB/Swiss-Prot:67 Mitochondrial DNA depletion syndrome 4A: An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.

Related Diseases for Mitochondrial Dna Depletion Syndrome 4a

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Diseases related to Mitochondrial Dna Depletion Syndrome 4a via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 90)
idRelated DiseaseScoreTop Affiliating Genes
1breast cancer10.5
2adrenoleukodystrophy10.4
3balo concentric sclerosis10.4
4myelinoclastic diffuse sclerosis10.4
5mitochondrial encephalomyopathy10.4
6encephalomyopathy10.4
7hypotonia10.4
8alcoholic hepatitis10.3
9combined oxidative phosphorylation deficiency 2410.3
10hepatitis10.3
11neuronitis10.3
12relapsing-remitting multiple sclerosis10.2
13cerebritis10.2
14mitochondrial dna depletion syndrome 110.1
15lung cancer10.1
16hypotrichosis 710.1
17alcohol dependence10.1
18galactosemia10.1
19alcohol abuse10.1
20atherosclerosis10.1
21hepatitis a10.1
22substance abuse10.1
23thyroiditis10.1
24hypoxia10.1
25endotheliitis10.1
26combined oxidative phosphorylation deficiency 1410.1
27creutzfeldt-jakob disease10.1
28autoimmune hepatitis10.1
29liver disease10.1
30status epilepticus10.1
31hypoglycemia10.1
32cerebral degeneration10.1
33cerebral folate deficiency10.1
34prickle1-related progressive myoclonus epilepsy with ataxia10.1C10orf2, POLG
35autoimmune addison disease10.1C10orf2, POLG
36deafness, autosomal dominant 3010.0C10orf2, POLG
37mitochondrial dna depletion syndrome 310.0C10orf2, DGUOK
38mitochondrial dna depletion syndrome 710.0C10orf2, POLG
39cicatricial ectropion10.0C10orf2, POLG
403-beta-hydroxysteroid dehydrogenase, type ii, deficiency10.0
41prostate cancer10.0
42adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency10.0
43adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency10.0
4417-alpha-hydroxylase/17,20-lyase deficiency10.0
45testicular germ cell tumor10.0
46hemophilia a10.0
47hepatitis b10.0
48lymphoplasmacytic lymphoma10.0
49alcohol-related birth defect10.0
50hypermobility syndrome10.0

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 4a:



Diseases related to mitochondrial dna depletion syndrome 4a

Symptoms for Mitochondrial Dna Depletion Syndrome 4a

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Symptoms by clinical synopsis from OMIM:

203700

Clinical features from OMIM:

203700

Symptoms:

 51 10 (show all 11)
  • microcephaly
  • anomalies of eyes and vision
  • ataxia/incoordination/trouble of the equilibrium
  • movement disorder
  • hypotonia
  • hypertonia/spasticity/rigidity/stiffness
  • hemiplegia/diplegia/hemiparesia/limb palsy
  • seizures/epilepsy/absences/spasms/status epilepticus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • autosomal recessive inheritance
  • convulsions

HPO human phenotypes related to Mitochondrial Dna Depletion Syndrome 4a:

(show all 41)
id Description Frequency HPO Source Accession
1 microcephaly typical (50%) HP:0000252
2 abnormality of the eye typical (50%) HP:0000478
3 seizures typical (50%) HP:0001250
4 muscular hypotonia typical (50%) HP:0001252
5 hypertonia typical (50%) HP:0001276
6 incoordination typical (50%) HP:0002311
7 hemiplegia/hemiparesis typical (50%) HP:0004374
8 abnormality of movement typical (50%) HP:0100022
9 cognitive impairment typical (50%) HP:0100543
10 autosomal recessive inheritance HP:0000007
11 visual loss HP:0000572
12 abnormality of visual evoked potentials HP:0000649
13 dementia HP:0000726
14 ataxia HP:0001251
15 muscular hypotonia HP:0001252
16 global developmental delay HP:0001263
17 cerebellar atrophy HP:0001272
18 hypertonia HP:0001276
19 myoclonus HP:0001336
20 hepatic failure HP:0001399
21 bile duct proliferation HP:0001408
22 micronodular cirrhosis HP:0001413
23 microvesicular hepatic steatosis HP:0001414
24 failure to thrive HP:0001508
25 vomiting HP:0002013
26 increased serum lactate HP:0002151
27 gliosis HP:0002171
28 hepatomegaly HP:0002240
29 developmental regression HP:0002376
30 astrocytosis HP:0002446
31 neuronal loss in central nervous system HP:0002529
32 elevated hepatic transaminases HP:0002910
33 increased csf protein HP:0002922
34 ethylmalonic aciduria HP:0003219
35 paralysis HP:0003470
36 3-methylglutaconic aciduria HP:0003535
37 infantile onset HP:0003593
38 rapidly progressive HP:0003678
39 cerebral cortical neurodegeneration HP:0006964
40 epilepsia partialis continua HP:0012847
41 cortical visual impairment HP:0100704

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 4a

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 4a


Cochrane evidence based reviews: Diffuse Cerebral Sclerosis of Schilder

Genetic Tests for Mitochondrial Dna Depletion Syndrome 4a

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Genetic tests related to Mitochondrial Dna Depletion Syndrome 4a:

id Genetic test Affiliating Genes
1 Alpers-Huttenlocher Syndrome22 POLG
2 Progressive Sclerosing Poliodystrophy24

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4a

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MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 4a:

33
Liver, Cortex, Brain, Eye

Animal Models for Mitochondrial Dna Depletion Syndrome 4a or affiliated genes

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Publications for Mitochondrial Dna Depletion Syndrome 4a

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Variations for Mitochondrial Dna Depletion Syndrome 4a

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UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 4a:

67 (show all 18)
id Symbol AA change Variation ID SNP ID
1POLGp.Ala467ThrVAR_012155rs113994095
2POLGp.Thr251IleVAR_023664rs113994094
3POLGp.Pro587LeuVAR_023671rs113994096
4POLGp.Trp748SerVAR_023673
5POLGp.Tyr831CysVAR_023674rs4154971
6POLGp.Gly848SerVAR_023675
7POLGp.Arg232GlyVAR_058870
8POLGp.Leu244ProVAR_058872
9POLGp.Ala767AspVAR_058886
10POLGp.Gln879HisVAR_058890
11POLGp.Thr885SerVAR_058891
12POLGp.Thr914ProVAR_058892
13POLGp.Ala957ProVAR_058893
14POLGp.Arg1096HisVAR_058894
15POLGp.His1110TyrVAR_058895
16POLGp.His1134ArgVAR_058896
17POLGp.Lys1191AsnVAR_058898
18POLGp.Glu1136LysVAR_065092

Clinvar genetic disease variations for Mitochondrial Dna Depletion Syndrome 4a:

5
id Gene Variation Type Significance SNP ID Assembly Location
1POLGNM_002693.2(POLG): c.1399G> A (p.Ala467Thr)single nucleotide variantPathogenicrs113994095GRCh37Chr 15, 89870432: 89870432
2POLGNM_002693.2(POLG): c.2542G> A (p.Gly848Ser)single nucleotide variantPathogenicrs113994098GRCh37Chr 15, 89865023: 89865023
3POLGNM_002693.2(POLG): c.752C> T (p.Thr251Ile)single nucleotide variantPathogenicrs113994094GRCh37Chr 15, 89873415: 89873415
4POLGNM_002693.2(POLG): c.2617G> T (p.Glu873Ter)single nucleotide variantPathogenicrs121918047GRCh37Chr 15, 89864473: 89864473
5POLGNM_002693.2(POLG): c.2243G> C (p.Trp748Ser)single nucleotide variantPathogenicrs113994097GRCh37Chr 15, 89866657: 89866657
6POLGPOLG, TRP1020TERundetermined variantPathogenic
7POLGNM_002693.2(POLG): c.3218C> T (p.Pro1073Leu)single nucleotide variantPathogenicrs267606959GRCh37Chr 15, 89862217: 89862217
8POLGNM_002693.2(POLG): c.2243G> C (p.Trp748Ser)single nucleotide variantPathogenicrs113994097GRCh37Chr 15, 89866657: 89866657

Expression for genes affiliated with Mitochondrial Dna Depletion Syndrome 4a

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Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 4a.

Pathways for genes affiliated with Mitochondrial Dna Depletion Syndrome 4a

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Pathways related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.6POLG, POLG2
29.6POLG, POLG2

GO Terms for genes affiliated with Mitochondrial Dna Depletion Syndrome 4a

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Cellular components related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial nucleoidGO:00426459.3C10orf2, POLG, POLG2
2mitochondrial matrixGO:00057598.4C10orf2, DGUOK, PARS2, POLG2
3mitochondrionGO:00057397.6C10orf2, DGUOK, PARS2, POLG, POLG2

Biological processes related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1DNA-dependent DNA replicationGO:00062619.9POLG, POLG2
2mitochondrion organizationGO:00070059.8C10orf2, POLG2
3cellular response to glucose stimulusGO:00713339.7C10orf2, POLG
4DNA biosynthetic processGO:00718979.6POLG, POLG2
5mitochondrial DNA replicationGO:00062649.2C10orf2, POLG, POLG2
6nucleobase-containing small molecule metabolic processGO:00550869.0DGUOK, TYMP
7DNA replicationGO:00062608.0C10orf2, POLG, POLG2, TYMP

Molecular functions related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1DNA-directed DNA polymerase activityGO:00038879.6POLG, POLG2
2protease bindingGO:00020209.4C10orf2, POLG

Sources for Mitochondrial Dna Depletion Syndrome 4a

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet