MCID: MTC056
MIFTS: 43

Mitochondrial Dna Depletion Syndrome 4a malady

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

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 4a

About this section
Sources:
11Disease Ontology, 12diseasecard, 13DISEASES, 24GeneTests, 25Genetics Home Reference, 27GTR, 30ICD10, 31ICD10 via Orphanet, 37MedGen, 39MeSH, 40MESH via Orphanet, 45NCIt, 48NIH Rare Diseases, 49NINDS, 50Novoseek, 52OMIM, 54Orphanet, 62SNOMED-CT, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Mitochondrial Dna Depletion Syndrome 4a:

Name: Mitochondrial Dna Depletion Syndrome 4a 52 11 70 12
Alpers Syndrome 11 48 24 25 54 70 50 13 68
Alpers-Huttenlocher Syndrome 11 48 24 25 54 70
Alpers Progressive Infantile Poliodystrophy 11 48 24 25 70
Progressive Sclerosing Poliodystrophy 11 25 49 27
Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis 48 25 70
Progressive Neuronal Degeneration of Childhood with Liver Disease 24 54
Diffuse Cerebral Sclerosis of Schilder 25 68
Alpers Disease 48 25
Pndc 48 70
Neuronal Degeneration of Childhood with Liver Disease, Progressive 48
Neuronal Degeneration of Childhood with Liver Disease Progressive 70
 
Mitochondrial Dna Depletion Syndrome 4a Alpers Type 70
Alpers Progressive Sclerosing Poliodystrophy 54
Alpers' Disease or Gray-Matter Degeneration 11
Diffuse Cerebral Degeneration in Infancy 48
Progressive Cerebral Poliodystrophy 48
Poliodystrophia Cerebri Progressiva 48
Infantile Poliodystrophy 48
Alper's Syndrome 11
Alpers' Disease 49
Mtdps4a 70
Ahs 70

Characteristics:

Orphanet epidemiological data:

54
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:

64
mitochondrial dna depletion syndrome 4a:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset, rapidly progressive

Classifications:



External Ids:

OMIM52 203700
Disease Ontology11 DOID:0080122, DOID:1442
ICD1030 G31.81
MeSH39 D002549
NCIt45 C35257
SNOMED-CT62 20415001
Orphanet54 ORPHA726
ICD10 via Orphanet31 G31.8
MESH via Orphanet40 D002549
UMLS via Orphanet69 C0205710
MedGen37 C0205710

Summaries for Mitochondrial Dna Depletion Syndrome 4a

About this section
OMIM:52 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 tRNA Aminoacylation. Affiliated tissues include liver, cortex and brain.

Disease Ontology:11 A cerebral degeneration that results in progressive degeneration of grey matter in the cerebrum and has symptom convulsions.

UniProtKB/Swiss-Prot:70 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:49 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:25 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:48 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

Related Diseases for Mitochondrial Dna Depletion Syndrome 4a

About this section

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

(show all 40)
idRelated DiseaseScoreTop Affiliating Genes
1ah amyloidosis11.9
2adrenoleukodystrophy11.3
3tumefactive multiple sclerosis11.3
4pelizaeus-merzbacher disease11.2
5sudanophilic cerebral sclerosis11.2
6balo concentric sclerosis11.2
7myelinoclastic diffuse sclerosis11.2
8combined oxidative phosphorylation deficiency 2411.0
9hypotrichosis 711.0
10mitochondrial dna depletion syndrome 110.9
11combined oxidative phosphorylation deficiency 1410.8
123-beta-hydroxysteroid dehydrogenase, type ii, deficiency10.7
13adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency10.7
14adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency10.7
1517-alpha-hydroxylase/17,20-lyase deficiency10.7
16breast cancer10.1
17mitochondrial encephalomyopathy10.1
18encephalomyopathy10.1
19hypotonia10.1
20autosomal recessive myosclerosis myopathy10.0POLG, POLG2
21hepatitis9.8
22neuronitis9.8
23multiple epiphyseal dysplasia, autosomal dominant9.8POLG, TYMP
24cerebral degeneration9.8
25cerebritis9.8
26megalencephalic leukoencephalopathy with subcortical cysts9.7POLG, TYMP
27charcot-marie-tooth disease type 2t9.7POLG, TYMP
28creutzfeldt-jakob disease9.7
29autoimmune hepatitis9.7
30liver disease9.7
31status epilepticus9.7
32hypoglycemia9.7
33encephalopathy9.7
34mental retardation with spastic paraplegia9.6POLG, TYMP
35mucopolysaccharidosis9.6POLG, TYMP
36porencephaly9.4POLG, TYMP
37myoclonic epilepsy associated with ragged-red fibers9.4DARS2, POLG, TYMP
38mitochondrial neurogastrointestinal encephalopathy disease9.3DGUOK, POLG, TYMP
39ulceration of vulva9.0DGUOK, POLG, POLG2, TYMP
40mitochondrial recessive ataxia syndrome8.5DGUOK, 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 & Phenotypes for Mitochondrial Dna Depletion Syndrome 4a

About this section

Symptoms by clinical synopsis from OMIM:

203700

Clinical features from OMIM:

203700

Symptoms:

 11
  • convulsions

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 4a:

 64 54 (show all 47)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly64 54 typical (50%) Frequent (79-30%) HP:0000252
2 abnormality of the eye64 54 typical (50%) Frequent (79-30%) HP:0000478
3 seizures64 typical (50%) HP:0001250
4 muscular hypotonia64 54 typical (50%) Frequent (79-30%) HP:0001252
5 hypertonia64 typical (50%) HP:0001276
6 incoordination64 typical (50%) HP:0002311
7 hemiplegia/hemiparesis64 typical (50%) HP:0004374
8 abnormality of movement64 54 typical (50%) Frequent (79-30%) HP:0100022
9 cognitive impairment64 typical (50%) HP:0100543
10 visual loss64 HP:0000572
11 abnormality of visual evoked potentials64 HP:0000649
12 dementia64 HP:0000726
13 ataxia64 54 Frequent (79-30%) HP:0001251
14 global developmental delay64 54 Frequent (79-30%) HP:0001263
15 cerebellar atrophy64 HP:0001272
16 myoclonus64 54 Frequent (79-30%) HP:0001336
17 hepatic failure64 HP:0001399
18 bile duct proliferation64 HP:0001408
19 micronodular cirrhosis64 HP:0001413
20 microvesicular hepatic steatosis64 HP:0001414
21 failure to thrive64 HP:0001508
22 vomiting64 HP:0002013
23 increased serum lactate64 HP:0002151
24 gliosis64 HP:0002171
25 hepatomegaly64 HP:0002240
26 developmental regression64 54 Frequent (79-30%) HP:0002376
27 astrocytosis64 HP:0002446
28 neuronal loss in central nervous system64 HP:0002529
29 elevated hepatic transaminases64 HP:0002910
30 increased csf protein64 HP:0002922
31 ethylmalonic aciduria64 HP:0003219
32 paralysis64 HP:0003470
33 3-methylglutaconic aciduria64 HP:0003535
34 cerebral cortical neurodegeneration64 HP:0006964
35 epilepsia partialis continua64 HP:0012847
36 cortical visual impairment64 HP:0100704
37 abnormality of vision54 Frequent (79-30%)
38 blindness54 Occasional (29-5%)
39 spasticity54 Frequent (79-30%)
40 coma54 Frequent (79-30%)
41 choreoathetosis54 Frequent (79-30%)
42 areflexia54 Frequent (79-30%)
43 generalized tonic-clonic seizures54 Frequent (79-30%)
44 progressive spasticity54 Frequent (79-30%)
45 spastic paraparesis54 Frequent (79-30%)
46 paraparesis54 Frequent (79-30%)
47 focal seizures54 Frequent (79-30%)

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

About this section

Interventional clinical trials:

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

Genetic Tests for Mitochondrial Dna Depletion Syndrome 4a

About this section

Genetic tests related to Mitochondrial Dna Depletion Syndrome 4a:

id Genetic test Affiliating Genes
1 Progressive Sclerosing Poliodystrophy27
2 Alpers-Huttenlocher Syndrome24 POLG

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4a

About this section

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

36
Liver, Cortex, Brain, Eye

Publications for Mitochondrial Dna Depletion Syndrome 4a

About this section

Variations for Mitochondrial Dna Depletion Syndrome 4a

About this section

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

70 (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 (show all 12)
id Gene Variation Type Significance SNP ID Assembly Location
1POLGNM_002693.2(POLG): c.1399G> A (p.Ala467Thr)SNVPathogenicrs113994095GRCh37Chr 15, 89870432: 89870432
2POLGNM_002693.2(POLG): c.3151G> C (p.Gly1051Arg)SNVLikely pathogenic, Pathogenicrs121918049GRCh37Chr 15, 89862284: 89862284
3POLGNM_002693.2(POLG): c.2542G> A (p.Gly848Ser)SNVPathogenicrs113994098GRCh37Chr 15, 89865023: 89865023
4POLGNM_002693.2(POLG): c.752C> T (p.Thr251Ile)SNVPathogenicrs113994094GRCh37Chr 15, 89873415: 89873415
5POLGNM_002693.2(POLG): c.2617G> T (p.Glu873Ter)SNVPathogenicrs121918047GRCh37Chr 15, 89864473: 89864473
6POLGNM_002693.2(POLG): c.1760C> T (p.Pro587Leu)SNVPathogenicrs113994096GRCh37Chr 15, 89868870: 89868870
7POLGPOLG, TRP1020TERundetermined variantPathogenicChr na, -1: -1
8POLGNM_002693.2(POLG): c.2209G> C (p.Gly737Arg)SNVPathogenicrs121918054GRCh37Chr 15, 89866691: 89866691
9POLGNM_002693.2(POLG): c.3218C> T (p.Pro1073Leu)SNVPathogenicrs267606959GRCh37Chr 15, 89862217: 89862217
10POLGNM_002693.2(POLG): c.2243G> C (p.Trp748Ser)SNV, Phase unknownPathogenicrs113994097GRCh37Chr 15, 89866657: 89866657
11POLGNM_002693.2(POLG): c.2870C> T (p.Ala957Val)SNVLikely pathogenic, Pathogenicrs753160398GRCh37Chr 15, 89864108: 89864108
12POLGNM_002693.2(POLG): c.3612_3613insAACT (p.Gly1205Asnfs)insertionPathogenicrs886043241GRCh37Chr 15, 89860637: 89860638

Expression for genes affiliated with Mitochondrial Dna Depletion Syndrome 4a

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

Pathways for genes affiliated with Mitochondrial Dna Depletion Syndrome 4a

About this section

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

idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.3DARS2, FARS2

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

About this section

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

idNameGO IDScoreTop Affiliating Genes
1mitochondrial nucleoidGO:004264510.3POLG, POLG2
2mitochondrial matrixGO:00057599.1DARS2, DGUOK, FARS2, POLG2
3mitochondrionGO:00057397.9DARS2, DGUOK, FARS2, POLG, POLG2

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

idNameGO IDScoreTop Affiliating Genes
1DNA biosynthetic processGO:007189710.2POLG, POLG2
2DNA-dependent DNA replicationGO:000626110.1POLG, POLG2
3DNA replicationGO:00062609.7POLG2, TYMP
4tRNA aminoacylation for protein translationGO:00064189.3DARS2, FARS2

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

idNameGO IDScoreTop Affiliating Genes
1DNA-directed DNA polymerase activityGO:000388710.1POLG, POLG2
2tRNA bindingGO:00000499.3DARS2, FARS2

Sources for Mitochondrial Dna Depletion Syndrome 4a

About this section
2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet