MCID: GNT009
MIFTS: 50

Giant Axonal Neuropathy

Categories: Rare diseases, Neuronal diseases, Genetic diseases

Aliases & Classifications for Giant Axonal Neuropathy

MalaCards integrated aliases for Giant Axonal Neuropathy:

Name: Giant Axonal Neuropathy 23 49 24 50 36 28
Giant Axonal Neuropathy 1 49 69
Neuropathy, Giant Axonal 49 51
Gan 49 24
Giant Axonal Disease 24
Gan1 49

Classifications:



Summaries for Giant Axonal Neuropathy

NINDS : 50 Giant axonal neuropathy (GAN) is a rare inherited genetic disorder that affects both the central and peripheral nervous systems.  The majority of children with GAN will begin to show symptoms of the disease sometime before five years of age.  Signs of GAN usually begin in the peripheral nervous system, which controls movement and sensation in the arms, legs, and other parts of the body.  The typical symptoms of GAN are clumsiness and muscle weakness that progresses from a “waddling gait” to a pronounced difficulty in walking.  Additional symptoms include numbness or lack of feeling in the arms and legs, seizures, nystagmus (rapid back and forth movement of the eyes), and impaired cognitive development.  A characteristic sign of the disease is dull, tightly curled hair that is markedly different from the parents’ in color and texture. Researchers have discovered more than 20 different mutations associated with GAN in a gene, GAN1, which makes a protein called gigaxonin.   These mutations disrupt the regulation or production of gigaxonin in the nervous system.  As a result, axons, which are the long tails of neurons that allow them to communicate with other nerve cells, swell up with tangled filaments and become abnormally large.  Eventually these axons deteriorate and cause problems with movement and sensation since neurons are no longer able to communicate with each other.  Doctors diagnose GAN by using several tests, including one that measures nerve conduction velocity, a brain MRI, and a peripheral nerve biopsy (in which a bit of tissue from a peripheral nerve is removed and examined to look for swollen axons).  A definitive diagnosis using genetic testing is available on a research basis only.  GAN is inherited in an autosomal recessive pattern, which means that both parents of a child with GAN have to carry a copy of the mutated gene.   Parents, typically, will show no signs of the disease. 

MalaCards based summary : Giant Axonal Neuropathy, also known as giant axonal neuropathy 1, is related to giant axonal neuropathy 2 and axonal neuropathy, and has symptoms including intellectual disability, spasticity and areflexia. An important gene associated with Giant Axonal Neuropathy is GAN (Gigaxonin), and among its related pathways/superpathways are Proteoglycans in cancer and Platelet activation. The drugs Simvastatin and Hydroxymethylglutaryl-CoA Reductase Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and testes, and related phenotype is muscle.

Genetics Home Reference : 24 Giant axonal neuropathy is an inherited condition characterized by abnormally large and dysfunctional axons called giant axons. Axons are specialized extensions of nerve cells (neurons) that transmit nerve impulses. Symptoms of the disorder first become apparent in the peripheral nervous system, in which long axons connect the brain and spinal cord (central nervous system) to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. However, axons in the central nervous system are affected as well.

NIH Rare Diseases : 49 Giant axonal neuropathy (GAN) is a neurodegenerative disorder characterized by abnormally large and dysfunctional axons (the specialized extensions of nerve cells that are required for the transmission of nerve impulses). The condition typically appears in infancy or early childhood with severe peripheral motor and sensory neuropathy (affecting movement and sensation in the arms and legs). Early signs include difficulty walking, lack of coordination, and loss of strength. Over time, the central nervous system (brain and spinal cord) becomes involved, causing a gradual decline in mental function, loss of control of body movements, and seizures. Giant axonal neuropathy is caused by mutations in the GAN gene. It follows and autosomal dominant pattern of inheritance. Management is directed by a multidisciplinary team with the goal of optimizing intellectual and physical development. Last updated: 6/18/2015

GeneReviews: NBK1136

Related Diseases for Giant Axonal Neuropathy

Graphical network of the top 20 diseases related to Giant Axonal Neuropathy:



Diseases related to Giant Axonal Neuropathy

Symptoms & Phenotypes for Giant Axonal Neuropathy

Human phenotypes related to Giant Axonal Neuropathy:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 frequent (33%) HP:0001249
2 spasticity 31 frequent (33%) HP:0001257
3 areflexia 31 hallmark (90%) HP:0001284
4 generalized hypotonia 31 hallmark (90%) HP:0001290
5 abnormality of the cerebellum 31 frequent (33%) HP:0001317
6 joint hypermobility 31 hallmark (90%) HP:0001382
7 pes cavus 31 frequent (33%) HP:0001761
8 talipes equinovarus 31 frequent (33%) HP:0001762
9 woolly hair 31 frequent (33%) HP:0002224
10 pili canaliculi 31 hallmark (90%) HP:0002235
11 unsteady gait 31 frequent (33%) HP:0002317
12 difficulty walking 31 hallmark (90%) HP:0002355
13 distal muscle weakness 31 frequent (33%) HP:0002460
14 falls 31 occasional (7.5%) HP:0002527
15 scoliosis 31 frequent (33%) HP:0002650
16 genu valgum 31 occasional (7.5%) HP:0002857
17 distal sensory impairment 31 frequent (33%) HP:0002936
18 diffuse axonal swelling 31 hallmark (90%) HP:0003405
19 cns hypomyelination 31 hallmark (90%) HP:0003429
20 babinski sign 31 occasional (7.5%) HP:0003487
21 limb muscle weakness 31 occasional (7.5%) HP:0003690
22 proximal muscle weakness 31 hallmark (90%) HP:0003701
23 abnormality of the achilles tendon 31 hallmark (90%) HP:0005109
24 abnormal hand morphology 31 frequent (33%) HP:0005922
25 facial palsy 31 frequent (33%) HP:0010628
26 abnormality of the pituitary gland 31 occasional (7.5%) HP:0012503

UMLS symptoms related to Giant Axonal Neuropathy:


cerebellar signs, facial paresis, abnormal pyramidal signs, neuralgia

MGI Mouse Phenotypes related to Giant Axonal Neuropathy:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.1 ACTG1 ARHGEF1 ARHGEF12 BAG3 GAN VIM

Drugs & Therapeutics for Giant Axonal Neuropathy

Drugs for Giant Axonal Neuropathy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 1 79902-63-9 54454
2 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1
3 Anticholesteremic Agents Phase 1
4 Hypolipidemic Agents Phase 1
5 Antimetabolites Phase 1
6 Lipid Regulating Agents Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Simvatstatin Used to Treat Pulmonary Hypertension Unknown status NCT00538044 Phase 1 simvastatin
2 Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy Recruiting NCT02362438 Phase 1 Intrathecal Delivery of scAAV9/JeT-GAN
3 Giant Axonal Neuropathy Natural History Study Terminated NCT01503125

Search NIH Clinical Center for Giant Axonal Neuropathy

Genetic Tests for Giant Axonal Neuropathy

Genetic tests related to Giant Axonal Neuropathy:

# Genetic test Affiliating Genes
1 Giant Axonal Neuropathy 28 GAN

Anatomical Context for Giant Axonal Neuropathy

MalaCards organs/tissues related to Giant Axonal Neuropathy:

38
Brain, Spinal Cord, Testes, Eye, Skin, Pituitary, Cerebellum

Publications for Giant Axonal Neuropathy

Articles related to Giant Axonal Neuropathy:

(show top 50) (show all 125)
# Title Authors Year
1
Giant axonal neuropathy alters the structure of keratin intermediate filaments in human hair. ( 28424304 )
2017
2
Pili canaliculi as manifestation of giant axonal neuropathy. ( 28300918 )
2016
3
Intermediate filament aggregates cause mitochondrial dysmotility and increase energy demands in giant axonal neuropathy. ( 27000625 )
2016
4
Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease. ( 27369358 )
2016
5
A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer. ( 27023907 )
2016
6
Abnormal intermediate filament organization alters mitochondrial motility in giant axonal neuropathy fibroblasts. ( 26700320 )
2016
7
Kelch Domain of Gigaxonin Interacts with Intermediate Filament Proteins Affected in Giant Axonal Neuropathy. ( 26460568 )
2015
8
Giant axonal neuropathy-like disease in an Alexandrine parrot (Psittacula eupatria). ( 26330398 )
2015
9
A mild case of giant axonal neuropathy without central nervous system manifestation. ( 26381321 )
2015
10
Atypical giant axonal neuropathy arising from a homozygous mutation by uniparental isodisomy. ( 25040701 )
2014
11
Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy. ( 24860645 )
2014
12
Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin. ( 25398950 )
2014
13
Measuring Disease Progression in Giant Axonal Neuropathy: Implications for Clinical Trial Design. ( 25186661 )
2014
14
Giant axonal neuropathy: An updated perspective on its pathology and pathogenesis. ( 24947478 )
2014
15
Giant axonal neuropathy: a clinicoradiopathologic diagnosis. ( 24590247 )
2014
16
The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test. ( 24758703 )
2014
17
The absence of curly hair is associated with a milder phenotype in Giant Axonal Neuropathy. ( 23890932 )
2014
18
Giant Axonal Neuropathy. ( 25213662 )
2014
19
Giant axonal neuropathy: a rare inherited neuropathy with simple clinical clues. ( 25216920 )
2014
20
Unusual Neuroimaging Findings in Two Families with Giant Axonal Neuropathy. ( 26693541 )
2014
21
Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene. ( 23248352 )
2013
22
Heterogeneity of axonal pathology in Chinese patients with giant axonal neuropathy. ( 24273072 )
2013
23
Giant axonal neuropathy. ( 23931822 )
2013
24
Explaining intermediate filament accumulation in giant axonal neuropathy. ( 25003002 )
2013
25
Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy. ( 23316953 )
2013
26
Giant axonal neuropathy diagnosed on skin biopsy. ( 24211141 )
2013
27
A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family. ( 23332420 )
2013
28
Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. ( 23585478 )
2013
29
BAG3 mutations: another cause of giant axonal neuropathy. ( 22734908 )
2012
30
Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms. ( 22806374 )
2012
31
Clinicogenetical features of a Japanese patient with giant axonal neuropathy. ( 21356581 )
2012
32
Involvement of the globus pallidus in giant axonal neuropathy. ( 23044025 )
2012
33
Giant axonal neuropathy caused by compound heterozygosity for a maternally inherited microdeletion and a paternal mutation within the GAN gene. ( 20949505 )
2010
34
Giant axonal neuropathy: a pictorial essay and review of literature. ( 24148344 )
2010
35
Application of autologous bone marrow stem cells in giant axonal neuropathy. ( 22301809 )
2010
36
Clinical and genetic studies in a Chinese family with giant axonal neuropathy. ( 19295179 )
2009
37
Spectrum of magnetic resonance imaging findings in a family with giant axonal neuropathy confirmed by genetic studies. ( 19439850 )
2009
38
Phenotypic variability in giant axonal neuropathy. ( 19231187 )
2009
39
Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy. ( 19398414 )
2009
40
3T MR with diffusion tensor imaging and single-voxel spectroscopy in giant axonal neuropathy. ( 18581347 )
2008
41
Clinical, pathological and molecular findings in two siblings with giant axonal neuropathy (GAN): report from India. ( 18595793 )
2008
42
Genotype-phenotype analysis in patients with giant axonal neuropathy. ( 18343115 )
2008
43
Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN). ( 17587580 )
2007
44
Giant axonal neuropathy. ( 17256086 )
2007
45
Anesthesia for a child with giant axonal neuropathy. ( 17181534 )
2007
46
Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients. ( 17331252 )
2007
47
New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy. ( 17578852 )
2007
48
Giant axonal neuropathy: diffusion-weighted imaging features of the brain. ( 17005115 )
2006
49
Giant axonal neuropathy: clinical and genetic study in six cases. ( 15897506 )
2005
50
Giant axonal neuropathy in two siblings: clinical histopathological findings. ( 15696785 )
2005

Variations for Giant Axonal Neuropathy

ClinVar genetic disease variations for Giant Axonal Neuropathy:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 GAN NM_022041.3(GAN): c.1456G> A (p.Glu486Lys) single nucleotide variant Pathogenic rs119485088 GRCh37 Chromosome 16, 81399037: 81399037
2 GAN NM_022041.3(GAN): c.1447C> T (p.Gln483Ter) single nucleotide variant Pathogenic rs119485089 GRCh37 Chromosome 16, 81399028: 81399028
3 GAN GAN, 1-BP INS, 18A insertion Pathogenic
4 GAN NM_022041.3(GAN): c.601C> T (p.Arg201Ter) single nucleotide variant Pathogenic rs119485090 GRCh37 Chromosome 16, 81388328: 81388328
5 GAN NM_022041.3(GAN): c.1268T> C (p.Ile423Thr) single nucleotide variant Pathogenic rs119485091 GRCh37 Chromosome 16, 81398610: 81398610
6 GAN NM_022041.3(GAN): c.413G> A (p.Arg138His) single nucleotide variant Pathogenic rs119485092 GRCh37 Chromosome 16, 81388140: 81388140
7 GAN NM_022041.3(GAN): c.43C> A (p.Arg15Ser) single nucleotide variant Pathogenic rs119485093 GRCh37 Chromosome 16, 81348761: 81348761
8 GAN NM_022041.3(GAN): c.1429C> T (p.Arg477Ter) single nucleotide variant Pathogenic rs119485094 GRCh37 Chromosome 16, 81399010: 81399010
9 GAN NM_022041.3(GAN): c.505G> A (p.Glu169Lys) single nucleotide variant Pathogenic rs119485095 GRCh37 Chromosome 16, 81388232: 81388232
10 GAN NM_022041.3(GAN): c.851+1G> A single nucleotide variant Pathogenic rs747291494 GRCh37 Chromosome 16, 81390608: 81390608
11 GAN NM_022041.3(GAN): c.1502+1G> T single nucleotide variant Pathogenic GRCh37 Chromosome 16, 81399084: 81399084
12 GAN NM_022041.3(GAN): c.1157delA (p.Lys386Argfs) deletion Pathogenic GRCh38 Chromosome 16, 81363864: 81363864

Expression for Giant Axonal Neuropathy

Search GEO for disease gene expression data for Giant Axonal Neuropathy.

Pathways for Giant Axonal Neuropathy

Pathways related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.81 ACTG1 ARHGEF1 ARHGEF12
2 11.42 ACTG1 ARHGEF1 ARHGEF12
3 11.41 ACTG1 ARHGEF1 TUBB VIM
4
Show member pathways
11.17 ACTG1 TUBB VIM
5 10.76 ACTG1 VIM

GO Terms for Giant Axonal Neuropathy

Cellular components related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.93 ACTG1 ARHGEF1 ARHGEF12 BAG3 BCLAF1 CCT2
2 cytosol GO:0005829 9.7 ACTG1 ALMS1 ARHGEF1 ARHGEF12 BAG3 CCT2
3 extracellular matrix GO:0031012 9.02 ACTG1 CCT2 RPS10 TUBB VIM

Biological processes related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular process GO:0009987 8.96 MAP1B TUBB
2 movement of cell or subcellular component GO:0006928 8.8 ACTG1 TUBB VIM

Molecular functions related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.77 ACTG1 ALMS1 ARHGEF1 ARHGEF12 BAG3 BCLAF1
2 structural constituent of cytoskeleton GO:0005200 8.8 ACTG1 TUBB VIM

Sources for Giant Axonal Neuropathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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