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

About this section
Sources:
49OMIM, 10Disease Ontology, 11diseasecard, 67UniProtKB/Swiss-Prot, 23Genetics Home Reference, 65UMLS, 45NIH Rare Diseases, 22GeneTests, 47Novoseek, 12DISEASES, 51Orphanet, 46NINDS, 24GTR, 27ICD10, 36MeSH, 42NCIt, 59SNOMED-CT, 37MESH via Orphanet, 66UMLS via Orphanet, 28ICD10 via Orphanet, 34MedGen, 61The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Mitochondrial Dna Depletion Syndrome 4a:

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

Characteristics:

Orphanet epidemiological data:

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

HPO:

61
mitochondrial dna depletion syndrome 4a:
Onset and clinical course: rapidly progressive, infantile onset
Inheritance: autosomal recessive inheritance


Classifications:



External Ids:

OMIM49 203700
Disease Ontology10 DOID:0080122, DOID:1442
ICD1027 G31.81
MeSH36 D002549
NCIt42 C35257
SNOMED-CT59 20415001
Orphanet51 726
MESH via Orphanet37 D002549
UMLS via Orphanet66 C0205710
ICD10 via Orphanet28 G31.8
MedGen34 C0205710
UMLS65 C0205710

Summaries for Mitochondrial Dna Depletion Syndrome 4a

About this section
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 ah amyloidosis and adrenoleukodystrophy, and has symptoms including cognitive impairment, abnormality of movement and hemiplegia/hemiparesis. An important gene associated with Mitochondrial Dna Depletion Syndrome 4a is POLG (Polymerase (DNA) Gamma, Catalytic Subunit), and among its related pathways are Nucleotide Metabolism and Cell Cycle Control of Chromosomal Replication. Affiliated tissues include liver, brain and cortex.

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

About this section

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

(show top 50)    (show all 74)
idRelated DiseaseScoreTop Affiliating Genes
1ah amyloidosis12.3
2adrenoleukodystrophy11.9
3balo concentric sclerosis11.9
4myelinoclastic diffuse sclerosis11.7
5hypotrichosis 711.4
63-beta-hydroxysteroid dehydrogenase, type ii, deficiency11.3
7adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency11.3
8adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency11.3
917-alpha-hydroxylase/17,20-lyase deficiency11.3
10neuronitis10.6
11combined oxidative phosphorylation deficiency 2410.5
12mitochondrial dna depletion syndrome 110.4
13combined oxidative phosphorylation deficiency 1410.4
14lung cancer10.2
15autoimmune addison disease10.1C10orf2, POLG
16prickle1-related progressive myoclonus epilepsy with ataxia10.1C10orf2, POLG
17neuroblastoma10.1
18coronary artery disease10.1
19obesity10.1
20myelodysplastic syndrome10.1
21ataxia-telangiectasia10.1
22panic disorder10.1
23hepatitis10.1
24insulinoma10.1
25leukemia10.1
26artery disease10.1
27dermatomyositis10.1
28pertussis10.1
29arachnoiditis10.1
30hepatitis c10.1
31melanoma10.1
32cholecystitis10.1
33acalculous cholecystitis10.1
34purpura10.1
35cerebritis10.1
36tick infestation10.1
37ludwig's angina10.1
38dystonia10.1
39pneumonia10.1
40central pontine myelinolysis10.1
41childhood leukemia10.1
42molluscum contagiosum10.1
43cholangitis10.1
44sheehan syndrome10.1
45arachnoid cysts10.1
46glioma10.1
47growth hormone deficiency10.1
48torsion dystonia10.1
49ataxia10.1
50head injury10.1

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

About this section

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

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 Alpers-Huttenlocher Syndrome22 POLG

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4a

About this section

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

33
Liver, Brain, Cortex, Eye

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

About this section

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:

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

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

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:00426459.6POLG, POLG2

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

idNameGO IDScoreTop Affiliating Genes
1organelle organizationGO:00069969.2C10orf2, POLG2
2DNA replicationGO:00062609.1C10orf2, POLG, POLG2

Sources for Mitochondrial Dna Depletion Syndrome 4a

About this section
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