AHC
MCID: ALT001
MIFTS: 58

Alternating Hemiplegia of Childhood (AHC) malady

Genetic diseases, Rare diseases, Neuronal diseases categories

Summaries for Alternating Hemiplegia of Childhood

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22Genetics Home Reference, 44NIH Rare Diseases, 45NINDS, 66Wikipedia, 48OMIM, 34MalaCards
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NINDS:45 Alternating hemiplegia is a rare neurological disorder that develops in childhood, most often before the child is 18 months old. The disorder is characterized by recurrent episodes of paralysis that involve one or both sides of the body, multiple limbs, or a single limb. The paralysis may affect different parts of the body at different times and may be brief or last for several days. Oftentimes these episodes will resolve after sleep. Affected children may also have abnormal movements involving stiffening or "dance-like" movements of a limb, as well as walking and balance problems. Some children have seizures. Children may have normal or delayed development. There are both benign and more serious forms of the disorder. Most children do not have a family history of the disorder; however, recent studies have show that some children with a family history have mutations in the genes CACNA1A, SCN1A, and ATP1A2. Mutations in the ATP1A2 gene have previously been associated with families affect by familial hemiplegic migraine.

MalaCards: Alternating Hemiplegia of Childhood, also known as alternating hemiplegia syndrome, is related to hemiplegia and hemiplegic migraine. An important gene associated with Alternating Hemiplegia of Childhood is ATP1A2 (ATPase, Na+/K+ transporting, alpha 2 polypeptide), and among its related pathways are Cardiac muscle contraction and Hepatic ABC Transporters. The compounds lithium carbonate and ouabain have been mentioned in the context of this disorder. Affiliated tissues include eye and skeletal muscle, and related mouse phenotypes are respiratory system and integument.

Genetics Home Reference:22 Alternating hemiplegia of childhood is a neurological condition characterized by recurrent episodes of temporary paralysis, often affecting one side of the body (hemiplegia). During some episodes, the paralysis alternates from one side of the body to the other or affects both sides at the same time. These episodes begin in infancy or early childhood, usually before 18 months of age, and the paralysis lasts from minutes to days.

NIH Rare Diseases:44 Alternating hemiplegia of childhood (ahc) is a severe disorder affecting the neurological system of children usually before 18 months of age. classic ahc causes recurrent episodes of paralysis (hemiplegia) that involve one or both sides of the body, multiple limbs, or a single limb. the paralysis may affect different parts of the body at different times and may be brief or last for several days. symptoms disappear during sleep and return upon waking. the majority of affected children display some degree of developmental delay, abnormal eye (oculomotor) movements, uncontrolled limb movements (including ataxia, dystonia, and choreoathetosis) and seizures that occur in up to 50% of patients.  treatment options are limited to therapies that can help with some of the symptoms. the majority of cases of classic ahc are caused by new mutation in the atp1a3 gene that is not inherited. thus, most patients with ahc with a mutation in atp1a3 gene do not have a family history of the disorder.  additional genes such as cacna1a and atp1a2 have been identified in some cases of ahc with an atypical clinical presentation.  atp1a2 mutations were shown, however, to be more consistent with familial hemiplegic migraine. last updated: 11/29/2012

Wikipedia:66 Alternating hemiplegia of childhood (AHC) is a rare neurological disorder of uncertain etiology, though... more...

Description from OMIM:48 104290,614820

Aliases & Classifications for Alternating Hemiplegia of Childhood

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9Disease Ontology, 10diseasecard, 44NIH Rare Diseases, 21GeneTests, 23GTR, 22Genetics Home Reference, 45NINDS, 48OMIM, 50Orphanet, 63UMLS, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

50
alternating hemiplegia of childhood:
Inheritance: Autosomal dominant,Sporadic; Age of onset: Neonatal/infancy; Age of death: Any age


Aliases & Descriptions:

alternating hemiplegia of childhood 9 10 44 21 23 22 48 50 63
alternating hemiplegia syndrome 44 22
alternating hemiplegia 44 45
ahc 44 50
alternating hemiplegia in childhood 50


External Ids:

Disease Ontology9 DOID:0050635
MESH via Orphanet37 C536589
ICD10 via Orphanet27 G98
SNOMED-CT via Orphanet60 230466004
UMLS via Orphanet64 C0338488

Related Diseases for Alternating Hemiplegia of Childhood

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18GeneCards, 19GeneDecks
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Diseases in the Alternating Hemiplegia of Childhood family:

Atp1a2-Related Alternating Hemiplegia of Childhood Atp1a3-Related Alternating Hemiplegia of Childhood
Alternating Hemiplegia of Childhood 2

Diseases related to Alternating Hemiplegia of Childhood via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 51)
idRelated DiseaseScoreTop Affiliating Genes
1hemiplegia31.8CACNA1A, ATP1A2, ATP1A3
2hemiplegic migraine30.9CACNA1A, ATP1A2
3familial hemiplegic migraine30.9CACNA1A, ATP1A2
4migraine30.7CALCA, ATP1A2, CACNA1A, TAC1, SLC1A3
5alternating hemiplegia of childhood 210.5
6acute hemorrhagic conjunctivitis10.5
7conjunctivitis10.5
8dystonia10.5
9benign familial nocturnal alternating hemiplegia of childhood10.5
10x-linked adrenal hypoplasia congenita10.4
11cerebritis10.4
12rapid-onset dystonia-parkinsonism10.4
13atp1a2-related alternating hemiplegia of childhood10.4
14atp1a3-related alternating hemiplegia of childhood10.4
15medial medullary syndrome10.3
16sporadic hemiplegic migraine10.2
17hypotonia10.2
18infantile hypotonia10.2
19amyloidosis10.2
20adrenal hypoplasia, congenital, with hypogonadotropic hypogonadism10.2
21monosomy xp2110.2
22episodic ataxia10.1SLC1A3
23movement disease10.1ATP1A3, SLC2A1
24migraine without aura10.0ATP1A2, CACNA1A
25quadriplegia10.0
26hemiplegia alterans10.0
27dermatitis10.0
28dosage-sensitive sex reversal10.0
29complex regional pain syndrome10.0TAC1, CALCA
30giant cell tumor10.0CALCA, MMP9
31mental retardation10.0SLC1A3, CACNA1A, ATP1A2
32cluster headache10.0CACNA1A, CALCA
33papillary carcinoma10.0SLC2A1, CALCA
34pain agnosia10.0CALCA, TAC1
35epilepsy syndrome10.0SLC2A1, CACNA1A, ATP1A2
36neuroendocrine tumor10.0CALCA, TAC1
37papillary thyroid carcinoma10.0CALCA, SLC2A1
38diarrhea10.0TAC1, CALCA
39thyroid cancer10.0CALCA, SLC2A1
40transitional cell carcinoma10.0MMP9, SLC2A1
41carcinoid syndrome10.0CALCA, TAC1
42breast cancer10.0MMP9, SLC2A1, TAC1
43astrocytoma10.0TAC1, SLC2A1, SLC1A3, MMP9
44hypertension9.9TAC1, CALCA, MMP9
45glioblastoma multiforme9.9TAC1, MMP9, SLC2A1, SLC1A3
46malignant glioma9.9MMP9, SLC1A3, TAC1, SLC2A1
47osteoarthritis9.9CALCA, MMP9, TAC1
48arthritis9.9CALCA, MMP9, TAC1
49neuropathy9.9CACNA1A, TAC1, CALCA
50schizophrenia9.9CACNA1A, TAC1, SLC2A1, SLC1A3

Graphical network of the top 20 diseases related to Alternating Hemiplegia of Childhood:



Diseases related to alternating hemiplegia of childhood

Symptoms for Alternating Hemiplegia of Childhood

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48OMIM
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Symptoms by clinical synopsis from OMIM:

104290

Clinical features from OMIM:

104290,614820

Drugs & Therapeutics for Alternating Hemiplegia of Childhood

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials
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Approved drugs:

Search CenterWatch for Alternating Hemiplegia of Childhood

Drug clinical trials:

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Search NIH Clinical Center for Alternating Hemiplegia of Childhood

Search CenterWatch for Alternating Hemiplegia of Childhood

Genetic Tests for Alternating Hemiplegia of Childhood

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21GeneTests, 23GTR
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Genetic tests related to Alternating Hemiplegia of Childhood:

id Genetic test Affiliating Genes
1 Alternating Hemiplegia of Childhood21 23 ATP1A3

Anatomical Context for Alternating Hemiplegia of Childhood

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34MalaCards
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MalaCards organs/tissues related to Alternating Hemiplegia of Childhood:

34
Eye, Skeletal muscle

Animal Models for Alternating Hemiplegia of Childhood or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Alternating Hemiplegia of Childhood:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053888.2CALCA, MMP9, ATP1A2, CACNA1A
2MP:00107717.6ATP1A2, MMP9, CACNA1A, CALCA, TAC1
3MP:00107687.0CALCA, CACNA1A, MMP9, ATP1A2, ATP1A3, SLC2A1
4MP:00036317.0SLC2A1, ATP1A3, SLC1A3, ATP1A2, MMP9, CACNA1A
5MP:00053766.9MMP9, SLC2A1, SLC1A3, CALCA, ATP1A3, CACNA1A
6MP:00053866.5SLC2A1, ATP1A3, ATP1A2, MMP9, CACNA1A, CALCA

Publications for Alternating Hemiplegia of Childhood

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53PubMed
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Articles related to Alternating Hemiplegia of Childhood:

(show top 50)    (show all 80)
idTitleAuthorsYear
1
Genotype-phenotype correlations in alternating hemiplegia of childhood. (24431296)
2014
2
Intermediate form between alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism. (24123283)
2014
3
Functional studies and proteomics in platelets and fibroblasts reveal a lysosomal defect with increased cathepsin-dependent apoptosis in ATP1A3 defective alternating hemiplegia of childhood. (23681173)
2013
4
Mutations in ATP1A3 cause alternating hemiplegia of childhood. (23043298)
2013
5
Lack of SLC2A1 (glucose transporter 1) mutations in 30 Italian patients with alternating hemiplegia of childhood. (22899793)
2013
6
Application of Magnetic Resonance Spectroscopy in Patients with Alternating Hemiplegia of Childhood: Findings on Metabolic Dysfunctions. (24356855)
2013
7
Caregiver's burden and psychosocial issues in alternating hemiplegia of childhood. (23672836)
2013
8
Benign nocturnal alternating hemiplegia of childhood: A new case with unusual findings. (23820111)
2013
9
Profiles of blood biomarkers in alternating hemiplegia of childhood--increased MMP-9 and decreased substance P indicates its pathophysiology. (21550738)
2012
10
Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. (22850527)
2012
11
Alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism are allelic disorders due to ATP1A3 gene mutations. (23460948)
2012
12
De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. (22842232)
2012
13
An 11-year follow-up study of neonatal-onset, bath-induced alternating hemiplegia of childhood in twins. (22378663)
2012
14
Child neurology: benign nocturnal alternating hemiplegia of childhood. (23109658)
2012
15
Absence of small-vessel abnormalities in alternating hemiplegia of childhood. (20826074)
2011
16
Clinical features of nine patients with alternating hemiplegia of childhood. (21449903)
2011
17
Child neurology: alternating hemiplegia of childhood. (20368625)
2010
18
Absence of mutation in the SLC2A1 gene in a cohort of patients with alternating hemiplegia of childhood (AHC). (21445818)
2010
19
International Classification of Functioning, Disability and Health in subjects with alternating hemiplegia of childhood. (19968522)
2009
20
Abnormal cerebral glucose metabolism in alternating hemiplegia of childhood. (18492605)
2009
21
Glut1 deficiency and alternating hemiplegia of childhood. (19996082)
2009
22
Alternating hemiplegia of childhood: early characteristics and evolution of a neurodevelopmental syndrome. (19254988)
2009
23
Benign nocturnal alternating hemiplegia of childhood: The first clinical report with paroxysmal events home-video recordings. (18618665)
2008
24
'Absence of T378N mutation of ATP1A2 gene in five patients with alternating hemiplegia of childhood'. (18811707)
2008
25
The treatment and management of alternating hemiplegia of childhood. (17880649)
2007
26
Alternating hemiplegia of childhood successfully treated with topiramate: 18 months of follow-up. (16401872)
2006
27
Topiramate: a new agent for patients with alternating hemiplegia of childhood. (17177149)
2006
28
Alternating hemiplegia of childhood: no mutations in the glutamate transporter EAAT1. (17236110)
2006
29
Brainstem dysfunction in alternating hemiplegia of childhood: a neurophysiological study. (16674759)
2006
30
Alternating hemiplegia of childhood: a study of neuropsychological functioning. (15788223)
2005
31
General anesthesia for a patient with alternating hemiplegia of childhood. (16326684)
2005
32
Alternating hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2. (15534763)
2004
33
Alternating hemiplegia of childhood: a syndrome inherited with an autosomal dominant trait. (14667076)
2003
34
Alpha[11C] methyl-L-typtophan positron emission tomography in patients with alternating hemiplegia of childhood. (12088079)
2002
35
Caesarean section under general anaesthetic in a woman with alternating hemiplegia of childhood. (15321538)
2002
36
Long-term effect of flunarizine on patients with alternating hemiplegia of childhood in Japan. (11504600)
2001
37
Alternating hemiplegia of childhood in half-sisters. (10695898)
2000
38
Is alternating hemiplegia of childhood (AHC) a variant of migraine? (11167894)
2000
39
Alternating hemiplegia of childhood: no mutations in the familial hemiplegic migraine CACNA1A gene. (11167897)
2000
40
Successful trial of amantadine hydrochloride for two patients with alternating hemiplegia of childhood. (11508550)
2000
41
Alternating hemiplegia of childhood or Hashimoto's encephalopathy? (10201439)
1999
42
Alternating hemiplegia of childhood: insights into its pathophysiology. (9477247)
1998
43
A case of alternating hemiplegia of childhood with cerebellar atrophy. (9682890)
1998
44
Alternating hemiplegia of childhood: treatment of attacks with chloral hydrate and niaprazine. (9039526)
1997
45
Alternating hemiplegia of childhood: report of a case having a long history. (9134195)
1997
46
Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood. (7574469)
1995
47
No structural or biochemical evidence for mitochondrial cytopathy in a case of alternating hemiplegia of childhood. (7979233)
1994
48
Evidence for mitochondrial dysfunction in patients with alternating hemiplegia of childhood. (8498840)
1993
49
Single-photon emission computed tomography investigations of alternating hemiplegia of childhood. (8335150)
1993
50
Alternating hemiplegia of childhood. (8496742)
1993

Variations for Alternating Hemiplegia of Childhood

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for Alternating Hemiplegia of Childhood:

65
id Symbol AA change Variation ID SNP ID
1ATP1A2p.Thr378AsnVAR_019934rs28934002

Clinvar genetic disease variations for Alternating Hemiplegia of Childhood:

1
id Gene Name Type Significance SNP ID Assembly Location
1ATP1A2NM_000702.3(ATP1A2): c.1133C> A (p.Thr378Asn)single nucleotide variantPathogenicrs28934002GRCh37Chr 1, 160098557: 160098557

Expression for genes affiliated with Alternating Hemiplegia of Childhood

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Alternating Hemiplegia of Childhood

Search GEO for disease gene expression data for Alternating Hemiplegia of Childhood.

Pathways for genes affiliated with Alternating Hemiplegia of Childhood

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51PathCards, 31KEGG, 54QIAGEN, 56Reactome, 39NCBI BioSystems Database, 13EMD Millipore, 52PharmGKB
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Pathways related to Alternating Hemiplegia of Childhood according to GeneCards/GeneDecks:

(show all 20)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.8ATP1A2, ATP1A3
2
Show member pathways
9.8ATP1A2, ATP1A3
3
Show member pathways
calcium transport I39
9.8ATP1A2, ATP1A3
49.8ATP1A2, ATP1A3
59.8ATP1A3, ATP1A2
69.8ATP1A3, ATP1A2
79.8ATP1A3, ATP1A2
89.8ATP1A3, ATP1A2
99.8ATP1A3, ATP1A2
109.8ATP1A3, ATP1A2
11
Show member pathways
9.8ATP1A3, ATP1A2
12
Show member pathways
Synaptic Vesicle Pathway39
9.3SLC1A3, CACNA1A, ATP1A2
13
Show member pathways
9.2ATP1A2, SLC2A1, ATP1A3
149.2ATP1A2, ATP1A3, SLC2A1
159.2ATP1A3, ATP1A2, SLC2A1
16
Show member pathways
9.2ATP1A3, ATP1A2, TAC1
179.2MMP9, CACNA1A
189.2SLC1A3, TAC1, ATP1A3
199.1SLC2A1, MMP9
20
Show member pathways
8.8ATP1A2, ATP1A3, SLC2A1, SLC1A3

Compounds for genes affiliated with Alternating Hemiplegia of Childhood

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62Tocris Bioscience, 46Novoseek, 12DrugBank, 30IUPHAR, 52PharmGKB, 25HMDB
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Compounds related to Alternating Hemiplegia of Childhood according to GeneCards/GeneDecks:

(show top 50)    (show all 55)
idCompoundScoreTop Affiliating Genes
1lithium carbonate6210.2ATP1A3, ATP1A2
2ouabain46 1210.9TAC1, ATP1A2
34-aminopyridine46 3010.9TAC1, CACNA1A
4rp6758046 3010.8CALCA, TAC1
5gr 7363246 6210.8CALCA, TAC1
6helospectin469.8CALCA, TAC1
7resiniferatoxin46 3010.8TAC1, CALCA
8cromakalim46 3010.7TAC1, CALCA
9guanethidine46 1210.7CALCA, TAC1
10i-app469.7CALCA, TAC1
11capsazepine62 46 3011.7TAC1, CALCA
12thiorphan46 30 1211.7TAC1, CALCA
13ng-nitro-l-arginine469.7CALCA, TAC1
14phosphoramidon46 1210.7TAC1, CALCA
15digoxin46 62 52 25 1213.7TAC1, ATP1A2, ATP1A3
16furosemide46 62 30 52 25 1214.6TAC1, CALCA
17captopril46 62 52 30 1213.6TAC1, CALCA
18methacholine46 52 1211.6CALCA, TAC1
19clonidine46 52 30 1212.5TAC1, CALCA
20alpha lipoic acid469.4SLC2A1, MMP9
21glibenclamide46 30 52 6212.4SLC2A1, CALCA
22zoledronic acid469.4CALCA, MMP9
23verapamil46 30 52 25 1213.4TAC1, CACNA1A, SLC2A1
24l-nmma469.4MMP9, TAC1
25malate469.4MMP9, SLC1A3
26atropine46 30 1211.3CALCA, TAC1
27prostaglandin f2alpha469.2SLC2A1, TAC1, CALCA
282-deoxyglucose46 1210.2CALCA, SLC2A1
29acetylcholine46 52 30 25 1213.2CALCA, CACNA1A, TAC1
30potassium46 25 1211.2TAC1, ATP1A3, ATP1A2, CACNA1A
31hydroxyproline46 25 1211.2MMP9, CALCA
32lactose46 1210.1MMP9, SLC2A1
33inositol469.1SLC1A3, SLC2A1, MMP9
34forskolin46 52 1211.1CALCA, SLC2A1, TAC1
35wortmannin469.1SLC2A1, MMP9, SLC1A3
36capsaicin46 3010.0TAC1, CALCA
37glutamine469.0TAC1, SLC1A3, SLC2A1, CACNA1A
38actinomycin d468.9SLC2A1, MMP9, TAC1
39epinephrine46 25 1210.9CALCA, MMP9, TAC1
40norepinephrine46 25 1210.9CALCA, TAC1, MMP9
41sodium46 259.8CACNA1A, TAC1, ATP1A3, SLC1A3, ATP1A2
42pge2468.7CALCA, TAC1, MMP9
43lactate468.7MMP9, CALCA, SLC2A1
44gaba468.6MMP9, SLC1A3, TAC1, SLC2A1
45cysteine468.6MMP9, SLC2A1, TAC1, SLC1A3
46dopamine46 30 25 1211.4SLC2A1, CALCA, MMP9, TAC1
47estrogen468.4MMP9, SLC2A1, TAC1, CALCA
48calcium46 52 25 1211.0CACNA1A, MMP9, ATP1A2, TAC1, CALCA
49adenylate468.0SLC1A3, MMP9, TAC1, CALCA, SLC2A1
50glutamate467.2CACNA1A, ATP1A2, MMP9, CALCA, TAC1, SLC1A3

GO Terms for genes affiliated with Alternating Hemiplegia of Childhood

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17Gene Ontology
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Cellular components related to Alternating Hemiplegia of Childhood according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sodium:potassium-exchanging ATPase complexGO:0058909.8ATP1A3, ATP1A2
2caveolaGO:0059019.6ATP1A2, SLC2A1
3cell projectionGO:0429959.3SLC1A3, CACNA1A
4neuronal cell bodyGO:0430258.5CACNA1A, CALCA, TAC1, SLC1A3
5plasma membraneGO:0058867.7SLC2A1, ATP1A3, ATP1A2, CACNA1A, TAC1, SLC1A3

Biological processes related to Alternating Hemiplegia of Childhood according to GeneCards/GeneDecks:

(show all 16)
idNameGO IDScoreTop Affiliating Genes
1neurotransmitter uptakeGO:00150410.0SLC1A3, ATP1A2
2ATP biosynthetic processGO:00675410.0ATP1A2, ATP1A3
3visual learningGO:0085429.9ATP1A3, ATP1A2
4adult locomotory behaviorGO:0083449.9ATP1A3, ATP1A2
5sodium ion transmembrane transportGO:0357259.8ATP1A3, ATP1A2
6neuromuscular process controlling balanceGO:0508859.7CACNA1A, SLC1A3
7positive regulation of ossificationGO:0457789.6CALCA, TAC1
8response to painGO:0482659.6CALCA, TAC1
9energy reserve metabolic processGO:0061129.5CACNA1A, SLC2A1
10regulation of insulin secretionGO:0507969.4SLC2A1, CACNA1A
11regulation of blood pressureGO:0082179.3ATP1A2, CALCA, TAC1
12embryo implantationGO:0075669.2CALCA, MMP9
13positive regulation of cytosolic calcium ion concentrationGO:0072049.2TAC1, CALCA, CACNA1A
14synaptic transmissionGO:0072689.2SLC1A3, TAC1, CACNA1A
15transmembrane transportGO:0550859.1SLC2A1, SLC1A3, ATP1A2, ATP1A3
16neuropeptide signaling pathwayGO:0072189.0CALCA, TAC1

Molecular functions related to Alternating Hemiplegia of Childhood according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sodium:potassium-exchanging ATPase activityGO:0053919.5ATP1A2, ATP1A3
2identical protein bindingGO:0428028.5SLC2A1, CALCA, MMP9

Products for genes affiliated with Alternating Hemiplegia of Childhood

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Sources for Alternating Hemiplegia of Childhood

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet