PNDC
MCID: ALP003
MIFTS: 61

Alpers Syndrome (PNDC) malady

Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Liver diseases categories
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Summaries for Alpers Syndrome

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Genetics Home Reference:21 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.

MalaCards based summary: Alpers Syndrome, also known as alpers-huttenlocher syndrome, is related to adrenoleukodystrophy and balo concentric sclerosis, and has symptoms including microcephaly, anomalies of eyes and vision and ataxia/incoordination/trouble of the equilibrium. An important gene associated with Alpers Syndrome is POLG (polymerase (DNA directed), gamma), and among its related pathways are tRNA Aminoacylation and Metabolism. The compounds abacavir and deoxyguanosine have been mentioned in the context of this disorder. Affiliated tissues include liver, brain and eye.

Disease Ontology:8 A cerebral degeneration that results in progressive degeneration of grey matter in the cerebrum and has symptom convulsions.

NIH Rare Diseases:42 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:43 Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical symptoms: psychomotor regression (dementia); seizures; and liver disease.

Wikipedia:65 Alpers\' disease, also called Alpers\' syndrome,progressive sclerosing poliodystrophy, and progressive... more...

Description from OMIM:46 203700

Aliases & Classifications for Alpers Syndrome

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Sources:
8Disease Ontology, 42NIH Rare Diseases, 21Genetics Home Reference, 10DISEASES, 44Novoseek, 48Orphanet, 62UMLS, 9diseasecard, 46OMIM, 22GTR, 43NINDS, 20GeneTests, 34MeSH, 39NCIt, 57SNOMED-CT, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Alpers Syndrome, Aliases & Descriptions:

Name: Alpers Syndrome 8 42 21 10 44 48 62
Alpers-Huttenlocher Syndrome 8 42 20 21 48 62
Progressive Sclerosing Poliodystrophy 8 22 21 43 62
Alpers Progressive Infantile Poliodystrophy 8 42 21 62
Mitochondrial Dna Depletion Syndrome 4a 8 9 46
Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis 42 21
Alpers' Disease 8 43
Alpers Disease 42 21
Pndc 42 62
Neuronal Degeneration of Childhood with Liver Disease, Progressive 42
 
Progressive Neuronal Degeneration of Childhood with Liver Disease 48
Alpers Progressive Sclerosing Poliodystrophy 48
Diffuse Cerebral Degeneration in Infancy 42
Diffuse Cerebral Sclerosis of Schilder 21
Poliodystrophia Cerebri Progressiva 42
Progressive Cerebral Poliodystrophy 42
Infantile Poliodystrophy 42
Gray-Matter Degeneration 8
Alper's Syndrome 8


Classifications:



Characteristics (Orphanet epidemiological data):

48
alpers syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


External Ids:

Disease Ontology8 DOID:1442
MeSH34 D002549
NCIt39 C35257
OMIM46 203700
SNOMED-CT57 20415001
MESH via Orphanet35 D002549
ICD10 via Orphanet26 G31.8
UMLS via Orphanet63 C0205710

Related Diseases for Alpers Syndrome

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Graphical network of the top 20 diseases related to Alpers Syndrome:



Diseases related to alpers syndrome

Symptoms for Alpers Syndrome

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Symptoms by clinical synopsis from OMIM:

203700

Clinical features from OMIM:

203700

Symptoms:

48 (show all 10)
  • 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

HPO human phenotypes related to Alpers Syndrome:

(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 vision 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 Alpers Syndrome

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Drug clinical trials:

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Search NIH Clinical Center for Alpers Syndrome

Genetic Tests for Alpers Syndrome

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Genetic tests related to Alpers Syndrome:

id Genetic test Affiliating Genes
1 Alpers-Huttenlocher Syndrome20 POLG
2 Progressive Sclerosing Poliodystrophy22

Anatomical Context for Alpers Syndrome

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MalaCards organs/tissues related to Alpers Syndrome:

32
Liver, Brain, Eye

Animal Models for Alpers Syndrome or affiliated genes

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Publications for Alpers Syndrome

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Articles related to Alpers Syndrome:

(show all 31)
idTitleAuthorsYear
1
Abnormalities in Glycogen Metabolism in a Patient with Alpers' Syndrome Presenting with Hypoglycemia. (24272679)
2013
2
Phenotypic and genotypic variability in Alpers syndrome. (22237560)
2012
3
Polymerase gamma deficiency (POLG): clinical course in a child with a two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh's encephalopathy. (22342071)
2012
4
Alpers syndrome: an unusual etiology of failure to thrive. (22849523)
2012
5
Complete Deletion of a POLG1 Allele in a Patient with Alpers Syndrome. (23430898)
2012
6
Alpers syndrome: the natural history of a case highlighting neuroimaging, neuropathology, and fat metabolism. (22114215)
2012
7
Molecular and biochemical characterisation of a novel mutation in POLG associated with Alpers syndrome. (21235791)
2011
8
Alpers syndrome with mutations in POLG: clinical and investigative features. (22000311)
2011
9
Gender variability in presentation with Alpers' syndrome: a report of eight patients from the UAE. (21305355)
2011
10
Application of oligonucleotide array CGH in the detection of a large intragenic deletion in POLG associated with Alpers Syndrome. (20708716)
2011
11
Juvenile-onset Alpers syndrome: interpreting MRI findings. (20385895)
2010
12
Alpers syndrome presenting with anatomopathological features of fulminant autoimmune hepatitis. (20582478)
2010
13
Proof of progression over time: finally fulminant brain, muscle, and liver affection in Alpers syndrome associated with the A467T POLG1 mutation. (18783964)
2009
14
De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome. (19501198)
2009
15
Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. (18294203)
2008
16
Alpers syndrome with prominent white matter changes. (17923349)
2008
17
Rapidly progressive neurological deterioration in a child with Alpers syndrome exhibiting a previously unremarkable brain MRI. (18991199)
2008
18
Molecular diagnosis of Alpers syndrome. (16545482)
2006
19
Alpers syndrome: progressive neuronal degeneration of children with liver disease. (17109792)
2006
20
POLG mutations and Alpers syndrome. (15929042)
2005
21
POLG mutations associated with Alpers syndrome and mitochondrial DNA depletion. (16130100)
2005
22
POLG mutations in Alpers syndrome. (16177225)
2005
23
Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. (16181814)
2005
24
Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers' syndrome? An analysis of a national surveillance study. (15146014)
2004
25
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. (15122711)
2004
26
Mitochondrial DNA depletion in Alpers syndrome. (15328560)
2004
27
Respiratory chain deficiency in Alpers syndrome. (11521212)
2001
28
Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome. (9894877)
1999
29
Brain MR imaging findings in two patients with Alpers' syndrome. (8959359)
1996
30
Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male. (8605737)
1995
31
Progressive neuronal degeneration of childhood (Alpers syndrome) with hepatic cirrhosis. (8444257)
1993

Variations for Alpers Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Alpers Syndrome:

64 (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 Alpers Syndrome:

6
id Gene Name 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.2617G> T (p.Glu873Ter)single nucleotide variantPathogenicrs121918047GRCh37Chr 15, 89864473: 89864473
4POLGNM_002693.2(POLG): c.2243G> C (p.Trp748Ser)single nucleotide variantPathogenicrs113994097GRCh37Chr 15, 89866657: 89866657
5POLGPOLG, TRP1020TERundetermined variantPathogenic
6POLGNM_002693.2(POLG): c.3218C> T (p.Pro1073Leu)single nucleotide variantPathogenicrs267606959GRCh37Chr 15, 89862217: 89862217

Expression for genes affiliated with Alpers Syndrome

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Expression patterns in normal tissues for genes affiliated with Alpers Syndrome

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Pathways for genes affiliated with Alpers Syndrome

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Pathways related to Alpers Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.0FARS2, DARS2
2
Show member pathways
8.7DGUOK, COX5A, POLG2, POLG

Compounds for genes affiliated with Alpers Syndrome

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Sources:
50PharmGKB, 44Novoseek, 11DrugBank, 24HMDB, 28IUPHAR
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Compounds related to Alpers Syndrome according to GeneCards/GeneDecks:

(show all 17)
idCompoundScoreTop Affiliating Genes
1abacavir50 44 1112.0POLG2, POLG
2deoxyguanosine44 2410.9DGUOK, POLG
3nevirapine44 50 1111.8POLG, COX5A
4dctp44 2410.8POLG, DGUOK
5lamivudine44 50 1111.8POLG, POLG2
6dgtp44 2410.8DGUOK, POLG
7ethidium bromide449.6COX5A, POLG
8parathion44 2410.5DGUOK, POLG
9nucleoside449.5POLG, POLG2, DGUOK
10diethyl dithiocarbamate449.5POLG, POLG2, COX5A
11zidovudine44 50 1111.5COX5A, POLG2, POLG
12didanosine44 50 1111.4DGUOK, COX5A, POLG
13thymidylate449.3POLG, DGUOK
14atp44 289.9POLG, POLG2, COX5A, DGUOK
15phosphoric acid44 249.9FARS2, POLG, DARS2
16pyrophosphate44 249.8FARS2, POLG, DARS2
17Adenosine triphosphate24 119.6DGUOK, FARS2, DARS2

GO Terms for genes affiliated with Alpers Syndrome

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Cellular components related to Alpers Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial nucleoidGO:0426458.9POLG2, POLG, C10orf2
2mitochondrial matrixGO:0057598.6DGUOK, FARS2, DARS2

Biological processes related to Alpers Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial DNA replicationGO:0062649.5POLG, C10orf2
2DNA-dependent DNA replicationGO:0062619.4POLG2, POLG
3tRNA aminoacylation for protein translationGO:0064189.0FARS2, DARS2

Molecular functions related to Alpers Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1DNA-directed DNA polymerase activityGO:0038879.7POLG, POLG2
2protease bindingGO:0020209.6C10orf2, POLG
3tRNA bindingGO:0000498.9FARS2, DARS2
4ATP bindingGO:0055247.8DGUOK, FARS2, C10orf2, DARS2

Products for genes affiliated with Alpers Syndrome

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  • Antibodies
  • Proteins
  • Lysates

Sources for Alpers Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet