MCID: MTC056
MIFTS: 45

Mitochondrial Dna Depletion Syndrome 4a malady

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

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 4a

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Sources:
50OMIM, 11Disease Ontology, 46NIH Rare Diseases, 23GeneTests, 24Genetics Home Reference, 47NINDS, 13DISEASES, 52Orphanet, 68UniProtKB/Swiss-Prot, 25GTR, 12diseasecard, 48Novoseek, 66UMLS, 28ICD10, 37MeSH, 43NCIt, 38MESH via Orphanet, 67UMLS via Orphanet, 29ICD10 via Orphanet, 35MedGen, 60SNOMED-CT, 62The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Mitochondrial Dna Depletion Syndrome 4a:

Name: Mitochondrial Dna Depletion Syndrome 4a 50 11 68 12
Alpers Syndrome 46 23 24 13 52 68 48 66
Alpers-Huttenlocher Syndrome 11 46 23 24 52 68
Alpers Progressive Infantile Poliodystrophy 11 46 23 24 68
Progressive Sclerosing Poliodystrophy 11 24 47 25
Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis 46 24 68
Progressive Neuronal Degeneration of Childhood with Liver Disease 23 52
Diffuse Cerebral Sclerosis of Schilder 24 66
Alpers Disease 46 24
Pndc 46 68
Neuronal Degeneration of Childhood with Liver Disease, Progressive 46
 
Neuronal Degeneration of Childhood with Liver Disease Progressive 68
Mitochondrial Dna Depletion Syndrome 4a Alpers Type 68
Alpers Progressive Sclerosing Poliodystrophy 52
Diffuse Cerebral Degeneration in Infancy 46
Progressive Cerebral Poliodystrophy 46
Poliodystrophia Cerebri Progressiva 46
Infantile Poliodystrophy 46
Alper's Syndrome 11
Alpers' Disease 47
Mtdps4a 68
Ahs 68

Characteristics:

Orphanet epidemiological data:

52
alpers syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: adolescent,adult,late childhood,young Adult

HPO:

62
mitochondrial dna depletion syndrome 4a:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset, rapidly progressive


Classifications:



External Ids:

OMIM50 203700
Disease Ontology11 DOID:0080122, DOID:1442
ICD1028 G31.81
MeSH37 D002549
NCIt43 C35257
SNOMED-CT60 20415001
Orphanet52 ORPHA726
MESH via Orphanet38 D002549
UMLS via Orphanet67 C0205710
ICD10 via Orphanet29 G31.8
MedGen35 C0205710

Summaries for Mitochondrial Dna Depletion Syndrome 4a

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OMIM:50 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 ah amyloidosis 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 (DNA Polymerase Gamma, Catalytic Subunit), and among its related pathways is Transcriptional activation of mitochondrial biogenesis. Affiliated tissues include liver, cortex and brain.

Disease Ontology:11 A mitochondiral metabolism disease that is characterized by progressive degeneration of grey matter in the cerebrum and has symptom intractable epilepsy, has symptom psychomotor regression, and has symptom liver disease.

NIH Rare Diseases:46 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

UniProtKB/Swiss-Prot:68 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.

NINDS:47 Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical symptoms: psychomotor regression (dementia); seizures; and liver disease.

Genetics Home Reference:24 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.

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 all 45)
idRelated DiseaseScoreTop Affiliating Genes
1ah amyloidosis12.1
2adrenoleukodystrophy11.5
3tumefactive multiple sclerosis11.5
4pelizaeus-merzbacher disease11.3
5sudanophilic cerebral sclerosis11.3
6balo concentric sclerosis11.3
7myelinoclastic diffuse sclerosis11.3
8hypotrichosis 711.0
93-beta-hydroxysteroid dehydrogenase, type ii, deficiency10.9
10adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency10.9
11adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency10.9
1217-alpha-hydroxylase/17,20-lyase deficiency10.9
13breast cancer10.2
14mitochondrial encephalomyopathy10.2
15encephalomyopathy10.2
16hypotonia10.2
17prop1-related combined pituitary hormone deficiency10.1C10orf2, POLG
18combined oxidative phosphorylation deficiency 2410.1
19deafness, autosomal dominant 3010.1C10orf2, POLG
20mitochondrial dna depletion syndrome 110.0
21hallucinogen abuse10.0C10orf2, POLG
22combined oxidative phosphorylation deficiency 1410.0
23hepatitis9.9
24neuronitis9.9
25colorectal adenocarcinoma9.9C10orf2, POLG
26cranial pseudosarcomatous fasciitis9.9C10orf2, POLG
27cerebral degeneration9.9
28cerebritis9.9
29multiple epiphyseal dysplasia, autosomal dominant9.9POLG, TYMP
30creutzfeldt-jakob disease9.8
31autoimmune hepatitis9.8
32liver disease9.8
33status epilepticus9.8
34hypoglycemia9.8
35encephalopathy9.8
36megalencephalic leukoencephalopathy with subcortical cysts9.8POLG, TYMP
37charcot-marie-tooth disease type 2t9.7POLG, TYMP
38autosomal recessive myosclerosis myopathy9.7C10orf2, POLG, POLG2
39porencephaly9.5POLG, TYMP
40mucopolysaccharidosis9.4C10orf2, POLG, TYMP
41myoclonic epilepsy associated with ragged-red fibers9.3POLG, TYMP
42mental retardation with spastic paraplegia9.3C10orf2, POLG, TYMP
43mitochondrial neurogastrointestinal encephalopathy disease8.9C10orf2, DGUOK, POLG, TYMP
44ulceration of vulva8.5C10orf2, DGUOK, POLG, POLG2, TYMP
45mitochondrial recessive ataxia syndrome7.9C10orf2, DGUOK, FARS2, POLG, POLG2, TYMP

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:

 11 52 (show all 22)
  • intractable epilepsy
  • psychomotor regression
  • liver disease
  • microcephaly
  • abnormality of the eye
  • abnormality of vision
  • blindness
  • ataxia
  • muscular hypotonia
  • spasticity
  • coma
  • global developmental delay
  • choreoathetosis
  • areflexia
  • myoclonus
  • generalized tonic-clonic seizures
  • progressive spasticity
  • spastic paraparesis
  • developmental regression
  • paraparesis
  • focal seizures
  • abnormality of movement

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

(show all 38)
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 visual loss HP:0000572
11 abnormality of visual evoked potentials HP:0000649
12 dementia HP:0000726
13 ataxia HP:0001251
14 muscular hypotonia HP:0001252
15 global developmental delay HP:0001263
16 cerebellar atrophy HP:0001272
17 hypertonia HP:0001276
18 myoclonus HP:0001336
19 hepatic failure HP:0001399
20 bile duct proliferation HP:0001408
21 micronodular cirrhosis HP:0001413
22 microvesicular hepatic steatosis HP:0001414
23 failure to thrive HP:0001508
24 vomiting HP:0002013
25 increased serum lactate HP:0002151
26 gliosis HP:0002171
27 hepatomegaly HP:0002240
28 developmental regression HP:0002376
29 astrocytosis HP:0002446
30 neuronal loss in central nervous system HP:0002529
31 elevated hepatic transaminases HP:0002910
32 increased csf protein HP:0002922
33 ethylmalonic aciduria HP:0003219
34 paralysis HP:0003470
35 3-methylglutaconic aciduria HP:0003535
36 cerebral cortical neurodegeneration HP:0006964
37 epilepsia partialis continua HP:0012847
38 cortical visual impairment HP:0100704

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 4a:


ataxia, hepatomegaly, myoclonus, vomiting, visual disturbance, unspecified visual loss

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

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 Progressive Sclerosing Poliodystrophy25
2 Alpers-Huttenlocher Syndrome23 POLG

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4a

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

34
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:

68 (show all 17)
id Symbol AA change Variation ID SNP ID
1POLGp.Ala467ThrVAR_012155rs113994095
2POLGp.Thr251IleVAR_023664rs113994094
3POLGp.Pro587LeuVAR_023671rs113994096
4POLGp.Trp748SerVAR_023673rs113994097
5POLGp.Gly848SerVAR_023675rs113994098
6POLGp.Arg232GlyVAR_058870
7POLGp.Leu244ProVAR_058872
8POLGp.Ala767AspVAR_058886
9POLGp.Gln879HisVAR_058890
10POLGp.Thr885SerVAR_058891
11POLGp.Thr914ProVAR_058892rs139590686
12POLGp.Ala957ProVAR_058893
13POLGp.Arg1096HisVAR_058894rs368435864
14POLGp.His1110TyrVAR_058895
15POLGp.His1134ArgVAR_058896
16POLGp.Lys1191AsnVAR_058898
17POLGp.Glu1136LysVAR_065092rs56047213

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.3151G> C (p.Gly1051Arg)single nucleotide variantPathogenicrs121918049GRCh37Chr 15, 89862284: 89862284
3POLGNM_002693.2(POLG): c.2542G> A (p.Gly848Ser)single nucleotide variantPathogenicrs113994098GRCh37Chr 15, 89865023: 89865023
4POLGNM_002693.2(POLG): c.752C> T (p.Thr251Ile)single nucleotide variantPathogenicrs113994094GRCh37Chr 15, 89873415: 89873415
5POLGNM_002693.2(POLG): c.2617G> T (p.Glu873Ter)single nucleotide variantPathogenicrs121918047GRCh37Chr 15, 89864473: 89864473
6POLGNM_002693.2(POLG): c.2243G> C (p.Trp748Ser)single nucleotide variantPathogenicrs113994097GRCh37Chr 15, 89866657: 89866657
7POLGPOLG, TRP1020TERundetermined variantPathogenic
8POLGNM_002693.2(POLG): c.2209G> C (p.Gly737Arg)single nucleotide variantPathogenicrs121918054GRCh37Chr 15, 89866691: 89866691
9POLGNM_002693.2(POLG): c.3218C> T (p.Pro1073Leu)single nucleotide variantPathogenicrs267606959GRCh37Chr 15, 89862217: 89862217
10POLGNM_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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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:00426459.4C10orf2, POLG, POLG2
2mitochondrial matrixGO:00057598.6C10orf2, DGUOK, FARS2, POLG2
3mitochondrionGO:00057397.9C10orf2, DGUOK, FARS2, POLG, POLG2

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

idNameGO IDScoreTop Affiliating Genes
1DNA-dependent DNA replicationGO:000626110.0POLG, POLG2
2cellular response to glucose stimulusGO:00713339.8C10orf2, POLG
3DNA biosynthetic processGO:00718979.6POLG, POLG2
4mitochondrion organizationGO:00070059.5C10orf2, POLG2
5mitochondrial DNA replicationGO:00062649.4C10orf2, POLG
6DNA replicationGO:00062608.9POLG2, 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:00020209.2C10orf2, POLG

Sources for Mitochondrial Dna Depletion Syndrome 4a

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet