ALXDRD
MCID: ALX003
MIFTS: 63

Alexander Disease (ALXDRD)

Categories: Eye diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Alexander Disease

MalaCards integrated aliases for Alexander Disease:

Name: Alexander Disease 57 11 24 19 42 52 58 75 73 28 12 5 43 14 71 33
Alexander's Disease 11 42 73 38
Demyelinogenic Leukodystrophy 42 75
Alexanders Leukodystrophy 19 71
Alxdrd 57 73
Axd 42 58
Megalencephaly in Infancy Accompanied by Progressive Spasticity and Dementia 19
Fibrinoid Degeneration of Astrocytes 42
Leukodystrophy with Rosenthal Fibers 42
Dysmyelinogenic Leukodystrophy 42
Alexander's Leukodystrophy 33
Alexander Disease Type Ii 58
Alexander Disease Type I 58
Alexanders Disease 53
Axd Type Ii 58
Axd Type I 58
Alx 42

Characteristics:


Inheritance:

Alexander Disease: Autosomal dominant 58 57
Alexander Disease Type Ii: Autosomal dominant 58

Prevelance:

<1/1000000 (Japan) 58

Age Of Onset:

Alexander Disease: All ages 58
Alexander Disease Type Ii: Adolescent,Adult,Childhood 58
Alexander Disease Type I: Infancy,Neonatal 58

Age Of Death:

Alexander Disease: any age 58
Alexander Disease Type Ii: adult 58

OMIM®:

57 (Updated 24-Oct-2022)
Miscellaneous:
average age of onset 6 months (range birth - 2 years)
death by age 5 (infantile form)
three variants distinguished by age of onset - infantile (onset before age 2), juvenile (onset in childhood), and adult
juvenile patients have slower clinical course with preserved intellect, bulbar signs, ataxia, and spasticity
adult patients have heterogeneous symptoms including some with relapsing-remitting symptoms similar to multiple sclerosis


GeneReviews:

24
Penetrance Penetrance appears to be nearly 100% in individuals with the infantile and juvenile forms [li et al 2002, messing & brenner 2003a, messing 2018]....

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Summaries for Alexander Disease

MedlinePlus Genetics: 42 Alexander disease is a rare disorder of the nervous system. It is one of a group of disorders, called leukodystrophies, that involve the destruction of myelin. Myelin is the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses could be disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay. Less frequently, onset occurs later in childhood (the juvenile form) or in adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia). Rarely, a neonatal form of Alexander disease occurs within the first month of life and is associated with severe intellectual disability and developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures.Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the brain and spinal cord (central nervous system).

MalaCards based summary: Alexander Disease, also known as alexander's disease, is related to leukodystrophy and multiple system atrophy 1, and has symptoms including muscle spasticity and seizures. An important gene associated with Alexander Disease is GFAP (Glial Fibrillary Acidic Protein), and among its related pathways/superpathways are Signaling by Receptor Tyrosine Kinases and Neuroscience. The drug Metronidazole has been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and eye, and related phenotypes are macrocephaly and intellectual disability

NINDS: 52 Alexander disease is one of a group of neurological conditions known as the leukodystrophies.  Leukodystrophies are disorders that result from abnormalities in myelin, the “white matter” that protects nerve fibers in the brain. In Alexander disease, the destruction of white matter is accompanied by the formation of Rosenthal fibers--abnormal clumps of protein that accumulate in non-nerve cells (astrocytes) in the brain.  The most common type of Alexander disease is the infantile form that usually begins during the first two years of life.  Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures. The juvenile form of Alexander disease has an onset between the ages of two and thirteen years.  These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control.  Adult-onset forms of Alexander disease are less common.  The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder. The disease occurs in both males and females, and there are no ethnic, racial, geographic, or cultural/economic differences in its distribution.  Alexander disease is a progressive and often fatal disease.

GARD: 19 Alexander disease is a type of leukodystrophy characterized by the destruction of the myelin sheath (the fatty covering that acts as an insulator around nerve fiber) and abnormal protein deposits known as Rosenthal fibers. Symptoms of the infantile form include an enlarged brain and head, seizures, stiffness in the arms and/or legs, intellectual disability, and delayed physical development. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination. Alexander disease is caused by genetic changes in the GFAP gene. While this condition is inherited in an autosomal dominant fashion, most cases result from new genetic changes in the gene.

OMIM®: 57 In decreasing order of frequency, 3 forms of Alexander disease (ALXDRD) are recognized, based on age of onset: infantile, juvenile, and adult. Younger patients typically present with seizures, megalencephaly, developmental delay, and spasticity. In older patients, bulbar or pseudobulbar symptoms predominate, frequently accompanied by spasticity. The disease is progressive, with most patients dying within 10 years of onset. Imaging studies of the brain typically show cerebral white matter abnormalities, preferentially affecting the frontal region (Gorospe et al., 2002). All 3 forms have been shown to be caused by mutations in the GFAP gene. (203450) (Updated 24-Oct-2022)

Orphanet 58 Alexander disease: A rare neurodegenerative disorder of the astrocytes comprised of two clinical forms: Alexander disease (AxD) type I and type II manifesting with various degrees of macrocephaly, spasticity, ataxia and seizures and leading to psychomotor regression and death.

Alexander disease type i: An astrogliopathy and the most severe and common form of Alexander disease (AxD), presenting before the age of 4 and characterized by seizures, megalencephaly and developmental delay with progressive deterioration.

Alexander disease type ii: An astrogliopathy and a form of Alexander disease (AxD) characterized by ataxia, bulbar symptoms, spastic paraparesis, palatal myoclonus, and autonomic symptoms.

UniProtKB/Swiss-Prot: 73 A rare disorder of the central nervous system. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death within the first decade. Infants with Alexander disease develop a leukodystrophy with macrocephaly, seizures, and psychomotor retardation. Patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. Histologically, Alexander disease is characterized by Rosenthal fibers, homogeneous eosinophilic inclusions in astrocytes.

Disease Ontology: 11 A leukodystrophy that is characterized by the destruction of white matter and the formation of Rosenthal fibers consisting of abnormal clumps of protein that accumulate in astrocytes.

Wikipedia: 75 Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions... more...

GeneReviews: NBK1172

Related Diseases for Alexander Disease

Diseases related to Alexander Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 268)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 31.8 PLP1 NDUFV1 GFAP CRYAB CRYAA
2 multiple system atrophy 1 30.2 RPS27A HTT GFAP CRYAB
3 movement disease 30.1 VIM RPS27A HTT GFAP
4 supranuclear palsy, progressive, 1 30.0 RPS27A HTT GFAP
5 central nervous system disease 29.9 PLP1 GFAP CRYAB CRYAA
6 ischemia 29.9 SLC1A2 MAPK14 HSPB1 GFAP CASP3
7 cerebral degeneration 29.9 PLP1 GFAP CRYAA
8 status epilepticus 29.8 SLC1A2 MTOR GFAP CASP3
9 motor neuron disease 29.6 SLC1A2 RPS27A HTT HSPB1 CRYAA
10 parkinson disease, late-onset 29.3 RPS27A MTOR MAPK14 HTT HSPB1 CRYAA
11 myopathy 28.9 VIM SYNM RPS27A PLEC NDUFV1 HTT
12 alzheimer disease, familial, 1 28.5 SLC1A2 RPS27A PLP1 MTOR MAPK14 HTT
13 amyotrophic lateral sclerosis 1 28.5 SLC1A2 RPS27A MTOR KCNJ10 HTT HSPB3
14 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.4
15 megalencephaly 10.4
16 spasticity 10.4
17 glioma susceptibility 1 10.3
18 pathologic nystagmus 10.3
19 myoclonus 10.3
20 exudative vitreoretinopathy 4 10.3 VIM MTOR
21 clear cell ependymoma 10.3 VIM GFAP
22 tremor 10.3
23 myopathy, myofibrillar, 3 10.3 SYNM PLEC CRYAB
24 early-onset lamellar cataract 10.3 CRYAB CRYAA
25 epidermolysis bullosa simplex 5a, ogna type 10.2 SYNM PLEC
26 cataract 16, multiple types 10.2 CRYAB CRYAA
27 epithelial basement membrane dystrophy 10.2 SYNM PLEC
28 subependymal giant cell astrocytoma 10.2 MTOR GFAP CRYAB
29 progressive bulbar palsy 10.2
30 hypotonia 10.2
31 adult respiratory distress syndrome 10.2
32 myopathy, myofibrillar, 2 10.2 PLEC CRYAB CRYAA
33 rhabdoid meningioma 10.2 VIM GFAP
34 autosomal recessive limb-girdle muscular dystrophy type 2q 10.2 SYNM PLEC
35 adult syndrome 10.2
36 encephalomalacia 10.2 SLC1A2 GFAP CASP3
37 spinal and bulbar muscular atrophy, x-linked 1 10.1 HTT HDAC6 CRYAA
38 proteasome-associated autoinflammatory syndrome 1 10.1
39 aceruloplasminemia 10.1
40 scoliosis 10.1
41 megalencephalic leukoencephalopathy with subcortical cysts 10.1
42 parkinsonism 10.1
43 hydrocephalus 10.1
44 paraplegia 10.1
45 myopathy, myofibrillar, 1 10.1 SYNM RPS27A PLEC CRYAB
46 retinal ischemia 10.1 HSPB1 GFAP CRYAA CASP3
47 early-onset nuclear cataract 10.1 CRYAB CRYAA
48 charcot-marie-tooth disease, axonal, type 2l 10.1 HSPB3 HSPB1 CRYAA
49 sexual sadism 10.1 HSPB3 HSPB2 HSPB1
50 astroblastoma 10.1 VIM GFAP

Graphical network of the top 20 diseases related to Alexander Disease:



Diseases related to Alexander Disease

Symptoms & Phenotypes for Alexander Disease

Human phenotypes related to Alexander Disease:

58 30 (show top 50) (show all 80)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000256
2 intellectual disability 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001249
3 spasticity 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001257
4 agenesis of corpus callosum 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001274
5 megalencephaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001355
6 failure to thrive 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001508
7 frontal bossing 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002007
8 nausea and vomiting 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002017
9 clonus 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002169
10 eeg abnormality 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002353
11 scoliosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002650
12 abnormal pyramidal sign 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0007256
13 large face 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0100729
14 seizure 30 Hallmark (90%) HP:0001250
15 ptosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0000508
16 nystagmus 58 30 Frequent (33%) Frequent (79-30%)
HP:0000639
17 diplopia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000651
18 emotional lability 58 30 Frequent (33%) Frequent (79-30%)
HP:0000712
19 hyperhidrosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0000975
20 ataxia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001251
21 dysarthria 58 30 Very rare (1%) Frequent (79-30%)
HP:0001260
22 gait disturbance 58 30 Frequent (33%) Frequent (79-30%)
HP:0001288
23 tremor 58 30 Frequent (33%) Frequent (79-30%)
HP:0001337
24 dysphonia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001618
25 dysphagia 58 30 Frequent (33%) Frequent (79-30%)
HP:0002015
26 constipation 58 30 Frequent (33%) Frequent (79-30%)
HP:0002019
27 hypothermia 58 30 Frequent (33%) Frequent (79-30%)
HP:0002045
28 tetraplegia 58 30 Frequent (33%) Frequent (79-30%)
HP:0002445
29 cerebral calcification 58 30 Frequent (33%) Frequent (79-30%)
HP:0002514
30 hypotension 58 30 Frequent (33%) Frequent (79-30%)
HP:0002615
31 kyphosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0002808
32 sleep apnea 58 30 Frequent (33%) Frequent (79-30%)
HP:0010535
33 facial palsy 58 30 Frequent (33%) Frequent (79-30%)
HP:0010628
34 recurrent singultus 58 30 Frequent (33%) Frequent (79-30%)
HP:0100247
35 aphasia 30 Frequent (33%) HP:0002381
36 depression 30 Frequent (33%) HP:0000716
37 high palate 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000218
38 hydrocephalus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000238
39 short neck 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000470
40 diabetes mellitus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000819
41 hypothyroidism 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000821
42 hypertension 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000822
43 precocious puberty 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000826
44 osteopenia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000938
45 sudden cardiac death 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001645
46 chorea 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002072
47 respiratory insufficiency 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002093
48 developmental regression 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002376
49 aqueductal stenosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002410
50 bowel incontinence 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002607

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Neurologic Central Nervous System:
seizures
spasticity
hydrocephalus
psychomotor regression
diffuse demyelination (increased signal intensity in t2-weighted images, especially frontal lobes)
more
Laboratory Abnormalities:
presence of rosenthal fibers (cytoplasmic inclusions) in astrocytes
presence of glial fibrillary acidic proteins (gfap) in astrocytes
elevated csf protein

Head And Neck Head:
progressive macrocephaly

Clinical features from OMIM®:

203450 (Updated 24-Oct-2022)

UMLS symptoms related to Alexander Disease:


muscle spasticity; seizures

GenomeRNAi Phenotypes related to Alexander Disease according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.15 BLZF1 CASP3 CRYAA CRYAB GFAP HDAC6
2 no effect GR00402-S-2 10.15 BLZF1 CASP3 CRYAB HSPB1 HSPB3 HTT

MGI Mouse Phenotypes related to Alexander Disease:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.13 CASP3 CRYAB GFAP HDAC6 HSPB1 HSPB3
2 nervous system MP:0003631 10.11 CASP3 GFAP HDAC6 HTT KCNJ10 MAPK14
3 normal MP:0002873 10.1 GFAP HDAC6 HSPB1 HTT MAPK14 MTOR
4 muscle MP:0005369 10.02 CASP3 CRYAB GFAP HTT MAPK14 MTOR
5 growth/size/body region MP:0005378 9.97 CASP3 GFAP HDAC6 HSPB1 HSPB2 HTT
6 cellular MP:0005384 9.83 CASP3 CRYAA CRYAB GFAP HDAC6 HSPB1
7 behavior/neurological MP:0005386 9.5 CASP3 CRYAB GFAP HDAC6 HSPB2 HTT

Drugs & Therapeutics for Alexander Disease

Drugs for Alexander Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Metronidazole Approved 443-48-1, 69198-10-3 4173

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients With Alexander Disease Recruiting NCT04849741 Phase 3 ION373;Placebo
2 The Myelin Disorders Biorepository Project and Global Leukodystrophy Initiative Clinical Trials Network Recruiting NCT03047369
3 Evaluation of Outcome Metrics in Alexander Disease Recruiting NCT02714764

Search NIH Clinical Center for Alexander Disease

Cochrane evidence based reviews: alexander disease

Genetic Tests for Alexander Disease

Genetic tests related to Alexander Disease:

# Genetic test Affiliating Genes
1 Alexander Disease 28 GFAP

Anatomical Context for Alexander Disease

Organs/tissues related to Alexander Disease:

MalaCards : Brain, Spinal Cord, Eye, Medulla Oblongata, Bone Marrow, Cortex, Cerebellum

Publications for Alexander Disease

Articles related to Alexander Disease:

(show top 50) (show all 568)
# Title Authors PMID Year
1
The Alexander disease-causing glial fibrillary acidic protein mutant, R416W, accumulates into Rosenthal fibers by a pathway that involves filament aggregation and the association of alpha B-crystallin and HSP27. 53 62 24 57 5
16826512 2006
2
Adult Alexander disease with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene. 53 62 24 57 5
12975300 2003
3
Identification of GFAP gene mutation in hereditary adult-onset Alexander's disease. 53 62 24 57 5
12447932 2002
4
Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. 62 24 57 5
15732097 2005
5
GFAP mutations and polymorphisms in 13 unrelated Italian patients affected by Alexander disease. 53 62 57 5
17894839 2007
6
Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation. 53 62 57 5
11567214 2001
7
Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. 53 62 57 5
11138011 2001
8
Propensity for paternal inheritance of de novo mutations in Alexander disease. 53 62 24 57
16365765 2006
9
Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord. 53 62 24 57
16505300 2006
10
Alexander-disease mutation of GFAP causes filament disorganization and decreased solubility of GFAP. 53 62 24 5
15840648 2005
11
Alexander disease with serial MRS and a new mutation in the glial fibrillary acidic protein gene. 62 57 5
14557587 2003
12
Juvenile Alexander disease with a novel mutation in glial fibrillary acidic protein gene. 62 57 5
12034796 2002
13
c.1289G>A (p.Arg430His) variant in the epsilon isoform of the GFAP gene in a patient with adult onset Alexander disease. 62 24 57
30048824 2019
14
Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant. 62 24 57
23634874 2013
15
Splice site, frameshift, and chimeric GFAP mutations in Alexander disease. 62 24 5
22488673 2012
16
Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis. 62 24 5
21533827 2011
17
GFAP mutations, age at onset, and clinical subtypes in Alexander disease. 62 24 5
21917775 2011
18
A case of sporadic adult Alexander disease presenting with acute onset, remission and relapse. 62 24 5
20562394 2010
19
Unusual variants of Alexander's disease. 62 24 57
15732098 2005
20
Alexander disease: diagnosis with MR imaging. 62 24 57
11237983 2001
21
An infantile case of Alexander disease unusual for its MRI features and a GFAP allele carrying both the p.Arg79His mutation and the p.Glu223Gln coding variant. 53 62 5
19444543 2009
22
Can MR imaging diagnose adult-onset Alexander disease? 53 62 5
18388212 2008
23
Adult-onset Alexander disease : report on a family. 53 62 5
18004641 2008
24
The functional alteration of mutant GFAP depends on the location of the domain: morphological and functional studies using astrocytoma-derived cells. 53 62 5
17318298 2007
25
Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. 53 62 5
17065456 2006
26
A novel GFAP mutation and disseminated white matter lesions: adult Alexander disease? 53 62 5
12944715 2003
27
Diagnosis of Alexander disease in a Japanese patient by molecular genetic analysis. 53 62 5
11587071 2001
28
Alexander disease evolution over time: data from an Italian cohort of pediatric-onset patients. 62 57
34865968 2021
29
Relative stabilities of wild-type and mutant glial fibrillary acidic protein in patients with Alexander disease. 62 5
31484723 2019
30
Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. 62 5
30355500 2018
31
A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. 62 5
26486469 2016
32
CSF and Blood Levels of GFAP in Alexander Disease 62 5
26478912 2015
33
Neuroimaging and clinical features in type II (late-onset) Alexander disease. 62 5
24306001 2014
34
Effects of a polymorphism in the GFAP promoter on the age of onset and ambulatory disability in late-onset Alexander disease. 62 5
23903069 2013
35
Alexander Disease: Report of Two Unrelated Infantile Form Cases, Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran. 62 5
24427505 2013
36
Follow-up study of 22 Chinese children with Alexander disease and analysis of parental origin of de novo GFAP mutations. 62 5
23364391 2013
37
GFAP expression as an indicator of disease severity in mouse models of Alexander disease. 62 5
23432455 2013
38
Cerebellar ataxia as the first manifestation of Alexander's disease. 62 5
22510744 2012
39
Late-onset Alexander disease with a V87L mutation in glial fibrillary acidic protein (GFAP) and calcifying lesions in the sub-cortex and cortex. 62 5
21822933 2012
40
Glial fibrillary acidic protein mutations in adult-onset Alexander disease: clinical features observed in 12 Japanese patients. 62 5
20849398 2011
41
Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes. 62 5
20448479 2010
42
[Adult onset Alexander disease with a novel variant (S398F) in the glial fibrillary acidic protein gene]. 62 5
19618846 2009
43
Suppression of GFAP toxicity by alphaB-crystallin in mouse models of Alexander disease. 62 57
19129171 2009
44
Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. 62 5
18684770 2008
45
Novel deletion mutation in GFAP gene in an infantile form of Alexander disease. 53 62 24
18054694 2008
46
A case of infantile Alexander disease diagnosed by magnetic resonance imaging and genetic analysis. 62 5
17383133 2007
47
Alexander disease with hypothermia, microcoria, and psychiatric and endocrine disturbances. 62 57
17438228 2007
48
A case of infantile Alexander disease accompanied by infantile spasms diagnosed by DNA analysis. 62 5
17043438 2006
49
Novel mutation of gene coding for glial fibrillary acidic protein in a Japanese patient with Alexander disease. 62 5
16168595 2006
50
Dominantly-inherited adult-onset leukodystrophy with palatal tremor caused by a mutation in the glial fibrillary acidic protein gene. 53 62 24
15390001 2004

Variations for Alexander Disease

ClinVar genetic disease variations for Alexander Disease:

5 (show top 50) (show all 117)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GFAP NP_002046.1(GFAP):p.Glu373Asp PROTEIN Pathogenic
190359 GRCh37:
GRCh38:
2 GFAP NP_002046.1(GFAP):p.Met415Ile PROTEIN Pathogenic
190364 GRCh37:
GRCh38:
3 GFAP NM_002055.5(GFAP):c.1171+475_1171+482delinsATC INDEL Pathogenic
190366 rs797044592 GRCh37: 17:42987501-42987508
GRCh38: 17:44910133-44910140
4 GFAP NP_002046.1:p.Phe261_Thr302del DEL Pathogenic
190369 GRCh37:
GRCh38:
5 GFAP NM_002055.5(GFAP):c.242C>A (p.Ala81Asp) SNV Pathogenic
637027 rs1597864461 GRCh37: 17:42992613-42992613
GRCh38: 17:44915245-44915245
6 GFAP NM_002055.5(GFAP):c.217A>G (p.Met73Val) SNV Pathogenic
1173085 GRCh37: 17:42992638-42992638
GRCh38: 17:44915270-44915270
7 GFAP NM_002055.5(GFAP):c.1111G>A (p.Glu371Lys) SNV Pathogenic
1199219 GRCh37: 17:42988620-42988620
GRCh38: 17:44911252-44911252
8 GFAP NM_002055.5(GFAP):c.1087A>G (p.Ile363Val) SNV Pathogenic
1685846 GRCh37: 17:42988644-42988644
GRCh38: 17:44911276-44911276
9 GFAP NM_002055.5(GFAP):c.715C>T (p.Arg239Cys) SNV Pathogenic
Not Provided
16167 rs58064122 GRCh37: 17:42990702-42990702
GRCh38: 17:44913334-44913334
10 GFAP NM_002055.5(GFAP):c.716G>A (p.Arg239His) SNV Pathogenic
Pathogenic
Not Provided
16168 rs59565950 GRCh37: 17:42990701-42990701
GRCh38: 17:44913333-44913333
11 GFAP NM_002055.5(GFAP):c.1246C>T (p.Arg416Trp) SNV Pathogenic
16169 rs121909717 GRCh37: 17:42985443-42985443
GRCh38: 17:44908075-44908075
12 GFAP NM_002055.5(GFAP):c.236G>A (p.Arg79His) SNV Pathogenic
Pathogenic
Not Provided
Not Provided
16170 rs59285727 GRCh37: 17:42992619-42992619
GRCh38: 17:44915251-44915251
13 GFAP NM_002055.5(GFAP):c.235C>T (p.Arg79Cys) SNV Pathogenic
Not Provided
16171 rs59793293 GRCh37: 17:42992620-42992620
GRCh38: 17:44915252-44915252
14 GFAP NM_002055.5(GFAP):c.262C>T (p.Arg88Cys) SNV Pathogenic
Pathogenic
16172 rs61622935 GRCh37: 17:42992593-42992593
GRCh38: 17:44915225-44915225
15 GFAP NM_002055.5(GFAP):c.226C>T (p.Leu76Phe) SNV Pathogenic
Not Provided
16174 rs57120761 GRCh37: 17:42992629-42992629
GRCh38: 17:44915261-44915261
16 GFAP NM_002055.5(GFAP):c.229A>T (p.Asn77Tyr) SNV Pathogenic
16175 rs58732244 GRCh37: 17:42992626-42992626
GRCh38: 17:44915258-44915258
17 GFAP NM_002055.5(GFAP):c.1086G>C (p.Glu362Asp) SNV Pathogenic
16176 rs121909718 GRCh37: 17:42988645-42988645
GRCh38: 17:44911277-44911277
18 GFAP NM_002055.5(GFAP):c.827G>T (p.Arg276Leu) SNV Pathogenic
16177 rs121909719 GRCh37: 17:42989119-42989119
GRCh38: 17:44911751-44911751
19 GFAP NM_002055.5(GFAP):c.1055T>C (p.Leu352Pro) SNV Pathogenic
16178 rs28932769 GRCh37: 17:42988676-42988676
GRCh38: 17:44911308-44911308
20 GFAP NM_002055.5(GFAP):c.234C>A (p.Asp78Glu) SNV Pathogenic
16179 rs121909720 GRCh37: 17:42992621-42992621
GRCh38: 17:44915253-44915253
21 GFAP NM_002055.5(GFAP):c.208C>T (p.Arg70Trp) SNV Pathogenic
66460 rs60343255 GRCh37: 17:42992647-42992647
GRCh38: 17:44915279-44915279
22 GFAP NM_002055.5(GFAP):c.218T>C (p.Met73Thr) SNV Pathogenic
Not Provided
Not Provided
190334 rs61060395 GRCh37: 17:42992637-42992637
GRCh38: 17:44915269-44915269
23 GFAP NM_002055.5(GFAP):c.259G>A (p.Val87Ile) SNV Pathogenic
Pathogenic
190339 rs267607518 GRCh37: 17:42992596-42992596
GRCh38: 17:44915228-44915228
24 GFAP NM_002055.5(GFAP):c.230A>G (p.Asn77Ser) SNV Pathogenic
66468 rs57590980 GRCh37: 17:42992625-42992625
GRCh38: 17:44915257-44915257
25 GFAP NM_002055.5(GFAP):c.791T>C (p.Leu264Pro) SNV Pathogenic
190346 rs797044579 GRCh37: 17:42989155-42989155
GRCh38: 17:44911787-44911787
26 GFAP NM_002055.5(GFAP):c.803C>A (p.Ala268Asp) SNV Pathogenic
190349 rs797044582 GRCh37: 17:42989143-42989143
GRCh38: 17:44911775-44911775
27 GFAP NM_002055.5(GFAP):c.988C>G (p.Arg330Gly) SNV Pathogenic
190352 rs267607513 GRCh37: 17:42988743-42988743
GRCh38: 17:44911375-44911375
28 GFAP NM_002055.5(GFAP):c.994G>A (p.Glu332Lys) SNV Pathogenic
66515 rs267607514 GRCh37: 17:42988737-42988737
GRCh38: 17:44911369-44911369
29 GFAP NM_002055.5(GFAP):c.1070T>C (p.Leu357Pro) SNV Pathogenic
66428 rs267607515 GRCh37: 17:42988661-42988661
GRCh38: 17:44911293-44911293
30 GFAP NM_002055.5(GFAP):c.1079A>T (p.Asp360Val) SNV Pathogenic
66431 rs62636501 GRCh37: 17:42988652-42988652
GRCh38: 17:44911284-44911284
31 GFAP NM_002055.5(GFAP):c.1085A>G (p.Glu362Gly) SNV Pathogenic
190357 rs797044588 GRCh37: 17:42988646-42988646
GRCh38: 17:44911278-44911278
32 GFAP NM_002055.5(GFAP):c.1193C>T (p.Ser398Phe) SNV Pathogenic
Not Provided
190363 rs267607508 GRCh37: 17:42985496-42985496
GRCh38: 17:44908128-44908128
33 GFAP NM_002055.5(GFAP):c.1154C>G (p.Ser385Cys) SNV Likely Pathogenic
Not Provided
190362 rs797044590 GRCh37: 17:42988000-42988000
GRCh38: 17:44910632-44910632
34 GFAP NM_002055.5(GFAP):c.252C>G (p.Ile84Met) SNV Likely Pathogenic
432046 rs571151302 GRCh37: 17:42992603-42992603
GRCh38: 17:44915235-44915235
35 GFAP NM_002055.5(GFAP):c.215A>G (p.Glu72Gly) SNV Likely Pathogenic
374303 rs1057518685 GRCh37: 17:42992640-42992640
GRCh38: 17:44915272-44915272
36 GFAP NM_002055.5(GFAP):c.1125C>G (p.Asn375Lys) SNV Likely Pathogenic
590968 rs1567773470 GRCh37: 17:42988606-42988606
GRCh38: 17:44911238-44911238
37 GFAP NM_002055.5(GFAP):c.706A>G (p.Lys236Glu) SNV Likely Pathogenic
1299244 GRCh37: 17:42990711-42990711
GRCh38: 17:44913343-44913343
38 GFAP NM_002055.5(GFAP):c.1235C>T (p.Thr412Ile) SNV Likely Pathogenic
803429 rs1597853099 GRCh37: 17:42985454-42985454
GRCh38: 17:44908086-44908086
39 GFAP NM_002055.5(GFAP):c.1171+473C>A SNV Likely Pathogenic
805942 rs775524073 GRCh37: 17:42987510-42987510
GRCh38: 17:44910142-44910142
40 GFAP NM_002055.5(GFAP):c.197G>A (p.Arg66Gln) SNV Conflicting Interpretations Of Pathogenicity
190332 rs797044569 GRCh37: 17:42992658-42992658
GRCh38: 17:44915290-44915290
41 GFAP NM_002055.5(GFAP):c.667G>C (p.Glu223Gln) SNV Uncertain Significance
66494 rs56679084 GRCh37: 17:42990750-42990750
GRCh38: 17:44913382-44913382
42 GFAP NM_002055.5(GFAP):c.1171+5G>A SNV Uncertain Significance
323610 rs759032212 GRCh37: 17:42987978-42987978
GRCh38: 17:44910610-44910610
43 GFAP NM_002055.5(GFAP):c.930G>A (p.Met310Ile) SNV Uncertain Significance
548570 rs755602073 GRCh37: 17:42988801-42988801
GRCh38: 17:44911433-44911433
44 GFAP NM_002055.5(GFAP):c.1171+144T>C SNV Uncertain Significance
930563 rs560230868 GRCh37: 17:42987839-42987839
GRCh38: 17:44910471-44910471
45 GFAP NM_002055.5(GFAP):c.1171+472G>C SNV Uncertain Significance
Not Provided
931895 rs748860341 GRCh37: 17:42987511-42987511
GRCh38: 17:44910143-44910143
46 GFAP NM_002055.5(GFAP):c.462-2A>G SNV Uncertain Significance
1029407 rs1338213981 GRCh37: 17:42991458-42991458
GRCh38: 17:44914090-44914090
47 GFAP NM_002055.5(GFAP):c.697G>A (p.Ala233Thr) SNV Uncertain Significance
1032795 rs1220287768 GRCh37: 17:42990720-42990720
GRCh38: 17:44913352-44913352
48 GFAP NM_002055.5(GFAP):c.793A>G (p.Thr265Ala) SNV Uncertain Significance
1064519 rs758250219 GRCh37: 17:42989153-42989153
GRCh38: 17:44911785-44911785
49 GFAP NM_002055.5(GFAP):c.989G>C (p.Arg330Pro) SNV Uncertain Significance
522797 rs983143417 GRCh37: 17:42988742-42988742
GRCh38: 17:44911374-44911374
50 GFAP NM_002055.5(GFAP):c.381C>T (p.Leu127=) SNV Uncertain Significance
323622 rs138320302 GRCh37: 17:42992474-42992474
GRCh38: 17:44915106-44915106

UniProtKB/Swiss-Prot genetic disease variations for Alexander Disease:

73 (show top 50) (show all 62)
# Symbol AA change Variation ID SNP ID
1 GFAP p.Leu76Phe VAR_017465 rs57120761
2 GFAP p.Asn77Tyr VAR_017466 rs58732244
3 GFAP p.Arg79Cys VAR_017467 rs59793293
4 GFAP p.Arg79His VAR_017468 rs59285727
5 GFAP p.Arg88Cys VAR_017469 rs61622935
6 GFAP p.Arg88Ser VAR_017470 rs61622935
7 GFAP p.Arg239Cys VAR_017471 rs58064122
8 GFAP p.Arg239His VAR_017472 rs59565950
9 GFAP p.Arg258Pro VAR_017474 rs61726468
10 GFAP p.Glu362Asp VAR_017475 rs121909718
11 GFAP p.Arg416Trp VAR_017476 rs121909717
12 GFAP p.Asp78Glu VAR_017477 rs121909720
13 GFAP p.Lys63Gln VAR_071517 rs60095124
14 GFAP p.Arg66Gln VAR_071518 rs797044569
15 GFAP p.Arg70Gln VAR_071519 rs267607510
16 GFAP p.Arg70Trp VAR_071520 rs60343255
17 GFAP p.Glu72Lys VAR_071521 rs267607523
18 GFAP p.Met73Lys VAR_071522 rs61060395
19 GFAP p.Met73Arg VAR_071523 rs61060395
20 GFAP p.Met73Thr VAR_071524 rs61060395
21 GFAP p.Met74Thr VAR_071525 rs267607504
22 GFAP p.Leu76Val VAR_071526 rs57120761
23 GFAP p.Asn77Lys VAR_071527
24 GFAP p.Asn77Ser VAR_071528 rs57590980
25 GFAP p.Asp78Asn VAR_071529 rs797044571
26 GFAP p.Arg79Gly VAR_071530 rs59793293
27 GFAP p.Arg79Leu VAR_071531 rs59285727
28 GFAP p.Arg79Pro VAR_071532 rs59285727
29 GFAP p.Tyr83His VAR_071533 rs267607506
30 GFAP p.Lys86Glu VAR_071534 rs797044573
31 GFAP p.Leu90Pro VAR_071535 rs59661476
32 GFAP p.Leu97Pro VAR_071536 rs59568967
33 GFAP p.Leu101Pro VAR_071537 rs267607516
34 GFAP p.Glu207Lys VAR_071540 rs267607500
35 GFAP p.Glu207Gln VAR_071541 rs267607500
36 GFAP p.Glu210Lys VAR_071542 rs57661783
37 GFAP p.Leu235Pro VAR_071543 rs60269890
38 GFAP p.Lys236Thr VAR_071544 rs267607525
39 GFAP p.Arg239Leu VAR_071545 rs59565950
40 GFAP p.Arg239Pro VAR_071546 rs59565950
41 GFAP p.Tyr242Asp VAR_071547 rs60551555
42 GFAP p.Ala253Gly VAR_071548 rs61726470
43 GFAP p.Tyr257Cys VAR_071549 rs267607505
44 GFAP p.Ala267Pro VAR_071550 rs797044581
45 GFAP p.Arg276Leu VAR_071551 rs121909719
46 GFAP p.Lys279Glu VAR_071552 rs58536923
47 GFAP p.Arg330Gly VAR_071553 rs267607513
48 GFAP p.Glu332Lys VAR_071554 rs267607514
49 GFAP p.Leu352Pro VAR_071555 rs28932769
50 GFAP p.Leu359Pro VAR_071556 rs267607511

Expression for Alexander Disease

Search GEO for disease gene expression data for Alexander Disease.

Pathways for Alexander Disease

GO Terms for Alexander Disease

Cellular components related to Alexander Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon GO:0030424 10 VIM SLC1A2 PLEC HTT HDAC6 CRYAB
2 intermediate filament GO:0005882 9.92 VIM SYNM PLEC GFAP
3 intermediate filament cytoskeleton GO:0045111 9.56 VIM SYNM PLEC GFAP
4 astrocyte projection GO:0097449 9.55 SLC1A2 KCNJ10 GFAP
5 contractile fiber GO:0043292 8.8 PLEC HSPB1 CRYAB

Biological processes related to Alexander Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to unfolded protein GO:0006986 9.95 HSPB3 HSPB2 HSPB1
2 regulation of macroautophagy GO:0016241 9.91 MTOR HDAC6 CASP3
3 response to amino acid GO:0043200 9.8 CASP3 MTOR SLC1A2
4 regulation of protein phosphorylation GO:0001932 9.76 MTOR HSPB1 HDAC6
5 D-aspartate import across plasma membrane GO:0070779 9.71 SLC1A2 GFAP
6 negative regulation of intracellular transport GO:0032387 9.67 CRYAB CRYAA
7 astrocyte development GO:0014002 9.63 VIM PLP1 GFAP
8 protein refolding GO:0042026 9.56 HSPB2 HSPB1 CRYAB CRYAA
9 response to heat GO:0009408 9.32 MTOR HSPB2 HSPB1 CRYAB CRYAA
10 intermediate filament-based process GO:0045103 9.26 VIM GFAP

Molecular functions related to Alexander Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural molecule activity GO:0005198 9.86 PLP1 PLEC CRYAB CRYAA
2 unfolded protein binding GO:0051082 9.76 HSPB2 HSPB1 CRYAB CRYAA
3 structural constituent of cytoskeleton GO:0005200 9.56 VIM SYNM PLEC GFAP
4 structural constituent of eye lens GO:0005212 9.23 VIM HSPB2 CRYAB CRYAA

Sources for Alexander Disease

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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