MJD
MCID: MCH002
MIFTS: 63

Machado-Joseph Disease (MJD)

Categories: Eye diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Machado-Joseph Disease

MalaCards integrated aliases for Machado-Joseph Disease:

Name: Machado-Joseph Disease 56 12 24 52 25 53 58 73 36 13 54 43 15 71
Sca3 56 12 24 52 25 58 73
Mjd 56 12 24 52 25 58 73
Spinocerebellar Ataxia Type 3 12 24 25 58
Spinocerebellar Ataxia 3 56 12 52 73
Azorean Disease 12 25 29 6
Nigrospinodentatal Degeneration 56 52 73
Azorean Neurologic Disease 56 52 73
Spinopontine Atrophy 56 52 71
Azorean Ataxia 24 25
Nigro-Spino-Dentatal Degeneration with Nuclear Ophthalmoplegia 58
Azorean Disease of the Nervous System 58
Spinocerebellar Ataxia 3; Sca3 56
Spinocerebellar Atrophy Type 3 52
Spinocerebellar Atrophy Iii 56
Spinocerebellar Atrophy 73
Disease, Machado-Joseph 39
Ataxia, Spinocerebellar 71
Machado Disease 58

Characteristics:

Orphanet epidemiological data:

58
spinocerebellar ataxia type 3
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide),1-9/100000 (Portugal),1-9/100000 (Japan); Age of onset: Adolescent,Adult,Childhood; Age of death: adult;

OMIM:

56
Miscellaneous:
genetic anticipation
progressive disorder
onset in third to fourth decade
wide clinical variability
normal alleles contain up to 44 repeats
pathogenic alleles contain 52 to 86 repeats
incomplete penetrance with 45 to 51 repeats

Inheritance:
autosomal dominant


HPO:

31
machado-joseph disease:
Inheritance autosomal dominant inheritance genetic anticipation
Onset and clinical course progressive


GeneReviews:

24
Penetrance A zone of cag trinucleotide repeat lengths that displays reduced penetrance is less firmly established in individuals with sca3 than in several other sca disorders caused by trinucleotide expansion. however, rare intermediate-length alleles of 45 to approximately 60 cag repeats may show reduced penetrance.

Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Machado-Joseph Disease

Genetics Home Reference : 25 Spinocerebellar ataxia type 3 (SCA3) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA3 include speech difficulties, uncontrolled muscle tensing (dystonia), muscle stiffness (spasticity), rigidity, tremors, bulging eyes, and double vision. People with this condition may experience sleep disorders such as restless leg syndrome or REM sleep behavior disorder. Restless leg syndrome is a condition characterized by numbness or tingling in the legs accompanied by an urge to move the legs to stop the sensations. REM sleep behavior disorder is a condition in which the muscles are active during the dream (REM) stage of sleep, so an affected person often acts out his or her dreams. These sleep disorders tend to leave affected individuals feeling tired during the day. Over time, individuals with SCA3 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle cramps, muscle twitches (fasciculations), and swallowing difficulties. Individuals with SCA3 may have problems with memory, planning, and problem solving. Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA3 eventually require wheelchair assistance. They usually survive 10 to 20 years after symptoms first appear.

MalaCards based summary : Machado-Joseph Disease, also known as sca3, is related to olivopontocerebellar atrophy and spinocerebellar ataxia 2, and has symptoms including ataxia, abnormality of extrapyramidal motor function and bradykinesia. An important gene associated with Machado-Joseph Disease is ATXN3 (Ataxin 3), and among its related pathways/superpathways are Protein processing in endoplasmic reticulum and Metabolism of proteins. The drugs Mexiletine and Anti-Arrhythmia Agents have been mentioned in the context of this disorder. Affiliated tissues include eye, tongue and brain, and related phenotypes are hyperreflexia and abnormal pyramidal sign

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by slow degeneration of the hindbrain and has material basis in expansion of CAG triplet repeats (glutamine) in the ATXN3 gene.

NIH Rare Diseases : 52 Spinocerebellar ataxia 3 (SCA3) is a rare, inherited form of ataxia . Signs and symptoms may begin between childhood and late adulthood and vary greatly. Symptoms may include slowly progressive clumsiness in the arms and legs; a manner of walking (gait) that may be mistaken for drunkenness; difficulty speaking and swallowing; impaired eye movements or vision; and lower limb spasticity . Some people with SCA3 develop dystonia or symptoms similar to those of Parkinson's disease ; twitching of the face or tongue; nerve damage (neuropathy); or problems with urination and the autonomic nervous system . SCA3 is caused by a mutation in the ATXN3 gene and inheritance is autosomal dominant . There is no medication that slows the progressive course of the disease; management aims to relieve some symptoms and improve quality of life. Life expectancy ranges from the mid-30s for those with the most severe forms, to a nearly normal life expectancy for those with milder forms.

OMIM : 56 Machado-Joseph disease, named for affected families of Azorean extraction, is an autosomal dominant progressive neurologic disorder characterized principally by ataxia, spasticity, and ocular movement abnormalities. Although independently described as a seemingly separate disorder, spinocerebellar ataxia-3 is now known to be the same as Machado-Joseph disease. Three classic clinical subtypes of MJD are recognized: type 1 with early onset and marked pyramidal and dystonic signs; type 2, or pure, with predominant cerebellar ataxia; and type 3 with later-onset and peripheral neuropathy (Franca et al., 2008). (109150)

NINDS : 53 Machado-Joseph disease (MJD), which is also called spinocerebellar ataxia type 3, is a rare hereditary ataxia (ataxia is a medical term meaning lack of muscle control). The disease is characterized by slowly progressive clumsiness and weakness in the arms and legs, spasticity, a staggering lurching gait easily mistaken for drunkenness, difficulty with speech and swallowing, involuntary eye movements, double vision, and frequent urination. Some individuals also have dystonia (sustained muscle contractions that cause twisting of the body and limbs, repetitive movements, abnormal postures, and rigidity) or symptoms similar to those of Parkinson's disease. Others have twitching of the face or tongue, or peculiar bulging eyes.  Almost all individuals with MJD experience vision problems, including double vision or blurred vision, loss of the ability to distinguish color and/or contrast, and inability to control eye movements.

KEGG : 36 Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is one of the most common hereditary ataxias and is distributed worldwide. MJD is an autosomal dominant neurodegenerative disorder, involving predominantly the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Minor, but more specific, features such as external progressive ophthalmoplegia (EPO), dystonia, intention fasciculation-like movements of facial and lingual muscles, as well as bulging eyes, may also be of major importance for the clinical diagnosis of MJD. The mean age at onset is around 40 years. MJD is associated with CAG repeat expansions in the ATXN3 gene. CAG repeat varies in size among affected persons. There is no effective treatment of ataxia. Case series and small controlled trials of several medications including antianxiolytics, antidepressants, and antiepileptics have shown limited efficacy.

UniProtKB/Swiss-Prot : 73 Spinocerebellar ataxia 3: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATX3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.

Wikipedia : 74 Machado-Joseph disease (MJD), also known as Machado-Joseph Azorean disease, Machado's disease, Joseph's... more...

GeneReviews: NBK1196

Related Diseases for Machado-Joseph Disease

Diseases in the Machado-Joseph Disease family:

Machado-Joseph Disease Type 1 Machado-Joseph Disease Type 3
Machado-Joseph Disease Type 2

Diseases related to Machado-Joseph Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 181)
# Related Disease Score Top Affiliating Genes
1 olivopontocerebellar atrophy 33.5 SNCA SLC6A3 RPS27A ATXN7 ATXN2
2 spinocerebellar ataxia 2 32.7 HTT CACNA1A ATXN7 ATXN3 ATXN2
3 sleep disorder 31.7 SNCA SLC6A3 HTR1A ATXN3
4 rem sleep behavior disorder 31.7 SNCA SLC6A3 RPS27A
5 tremor 31.4 SNCA PRKN ATXN2
6 spinocerebellar ataxia 6 31.1 CACNA1A ATXN7 ATXN3 ATXN2
7 primary cerebellar degeneration 30.9 CHERP CACNA1A ATXN3 ATXN2 ATXN1
8 spinocerebellar ataxia 1 30.8 HTT CHERP CACNA1A ATXN7 ATXN3 ATXN2
9 spinocerebellar ataxia 8 30.7 HTT ATXN7 ATXN3 ATXN2
10 choreatic disease 30.7 HTT ATXN7 ATXN3
11 friedreich ataxia 30.6 CACNA1A ATXN3 ATXN2 ATXN1
12 dystonia 30.6 SLC6A3 PRKN HTT CACNA1A ATXN7 ATXN3
13 aceruloplasminemia 30.6 SNCA SLC6A3 HTT CACNA1A ATXN7 ATXN3
14 motor neuron disease 30.6 VCP SNCA RPS27A PRKN HTR1A HSPB1
15 spinocerebellar ataxia 7 30.6 CHERP ATXN7 ATXN3 ATXN2 ATXN1
16 cerebellar disease 30.3 CACNA1A ATXN7 ATXN3 ATXN2 ATXN1
17 movement disease 30.2 SNCA SLC6A3 PRKN HTT CACNA1A ATXN3
18 restless legs syndrome 30.2 SNCA SLC6A3 PRKN LOC108663987 CACNA1A ATXN7
19 episodic ataxia 30.2 CACNA1A ATXN7 ATXN3 ATXN1
20 multiple system atrophy 1 30.0 SNCA SLC6A3 RPS27A PRKN HTT ATXN3
21 parkinson disease, late-onset 29.8 VCP SNCA SLC6A3 RPS27A PRKN HTT
22 hereditary ataxia 29.6 CACNA1A ATXN7 ATXN3 ATXN2 ATXN1 ATN1
23 dentatorubral-pallidoluysian atrophy 29.4 HTT CACNA1A ATXN7 ATXN3 ATXN2 ATXN1
24 spinocerebellar ataxia 17 29.2 CACNA1A ATXN7 ATXN3 ATXN2 ATXN1 ATN1
25 spinocerebellar ataxia 12 29.2 CACNA1A ATXN7 ATXN3 ATXN2 ATXN1 ATN1
26 huntington disease 29.1 SNCA SLC6A3 RPS27A HTT CHERP ATXN7
27 autosomal dominant cerebellar ataxia 28.9 VCP SNCA RPS27A PRKN LOC108663987 HTT
28 dementia 28.4 VCP SNCA SLC6A3 RPS27A PRKN HTT
29 amyotrophic lateral sclerosis 1 28.1 VCP SNCA SLC6A3 RPS27A PRKN HTT
30 machado-joseph disease type 1 12.6
31 machado-joseph disease type 3 12.6
32 machado-joseph disease type 2 12.6
33 spinocerebellar atrophy with pupillary paralysis 12.2
34 spinocerebellar ataxia, x-linked 3 12.0
35 spinocerebellar degeneration 11.9
36 spinocerebellar atrophy 11.9
37 ataxias and cerebellar or spinocerebellar degeneration 11.5
38 majeed syndrome 11.5
39 brachydactylous dwarfism mseleni type 11.4
40 ataxia and polyneuropathy, adult-onset 11.4
41 spinocerebellar ataxia, autosomal recessive 3 11.3
42 mohr-tranebjaerg syndrome 11.3
43 dystonia 11, myoclonic 11.2
44 spinocerebellar ataxia 18 11.2
45 neuropathy 10.9
46 kearns-sayre syndrome 10.9
47 pathologic nystagmus 10.9
48 peripheral nervous system disease 10.9
49 spasticity 10.8
50 muscular atrophy 10.7

Graphical network of the top 20 diseases related to Machado-Joseph Disease:



Diseases related to Machado-Joseph Disease

Symptoms & Phenotypes for Machado-Joseph Disease

Human phenotypes related to Machado-Joseph Disease:

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperreflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001347
2 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
3 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
4 diplopia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000651
5 dysarthria 58 31 very rare (1%) Very frequent (99-80%) HP:0001260
6 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
7 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
8 dystonia 58 31 very rare (1%) Very frequent (99-80%) HP:0001332
9 progressive external ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000590
10 proptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000520
11 clumsiness 58 31 hallmark (90%) Very frequent (99-80%) HP:0002312
12 abnormality of extrapyramidal motor function 58 31 hallmark (90%) Very frequent (99-80%) HP:0002071
13 progressive cerebellar ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002073
14 abnormality of temperature regulation 58 31 occasional (7.5%) Occasional (29-5%) HP:0004370
15 vocal cord paralysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001605
16 vestibular dysfunction 58 31 occasional (7.5%) Occasional (29-5%) HP:0001751
17 abnormal autonomic nervous system physiology 31 occasional (7.5%) HP:0012332
18 spasticity 31 very rare (1%) HP:0001257
19 ataxia 31 very rare (1%) HP:0001251
20 fasciculations 31 very rare (1%) HP:0002380
21 external ophthalmoplegia 31 very rare (1%) HP:0000544
22 parkinsonism 31 very rare (1%) HP:0001300
23 gaze-evoked nystagmus 31 very rare (1%) HP:0000640
24 ptosis 31 HP:0000508
25 dysphagia 31 HP:0002015
26 limb ataxia 31 HP:0002070
27 babinski sign 31 HP:0003487
28 urinary bladder sphincter dysfunction 31 HP:0002839
29 rigidity 31 HP:0002063
30 dementia 31 HP:0000726
31 truncal ataxia 31 HP:0002078
32 cerebellar atrophy 31 HP:0001272
33 bradykinesia 31 HP:0002067
34 distal amyotrophy 31 HP:0003693
35 absent achilles reflex 31 HP:0003438
36 gliosis 31 HP:0002171
37 postural instability 31 HP:0002172
38 impaired vibratory sensation 31 HP:0002495
39 supranuclear ophthalmoplegia 31 HP:0000623
40 spinocerebellar tract degeneration 31 HP:0002503
41 dilated fourth ventricle 31 HP:0002198
42 dysmetric saccades 31 HP:0000641
43 facial-lingual fasciculations 31 HP:0007089
44 chronic pain 31 HP:0012532
45 impaired horizontal smooth pursuit 31 HP:0001151
46 muscle spasm 31 HP:0003394
47 abnormal electrooculogram 31 HP:0030454

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
dysarthria
limb ataxia
rigidity
truncal ataxia
more
Abdomen Gastrointestinal:
dysphagia

Muscle Soft Tissue:
muscle cramps
fasciculations

Head And Neck Eyes:
diplopia
external ophthalmoplegia
supranuclear ophthalmoplegia
gaze-evoked nystagmus
dysmetric saccades
more
Neurologic Peripheral Nervous System:
peripheral neuropathy
decreased vibration sense
impaired thermal sense
decreased or absent ankle reflexes
distal muscular atrophy

Genitourinary Bladder:
sphincter disturbances

Clinical features from OMIM:

109150

UMLS symptoms related to Machado-Joseph Disease:


ataxia, abnormality of extrapyramidal motor function, bradykinesia, chronic pain, muscular fasciculation, muscle cramp, muscle rigidity, muscle spasticity, cerebellar ataxia, ataxia, truncal, abnormal pyramidal signs

MGI Mouse Phenotypes related to Machado-Joseph Disease:

45 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.37 AR ATN1 ATXN1 ATXN2 ATXN3 ATXN7
2 growth/size/body region MP:0005378 10.25 AR ATN1 ATXN1 ATXN2 ATXN7 BECN1
3 homeostasis/metabolism MP:0005376 10.25 AR ATN1 ATXN1 ATXN2 ATXN3 BECN1
4 cardiovascular system MP:0005385 10.18 AR ATN1 BECN1 HSPB1 HTR1A HTT
5 mortality/aging MP:0010768 10.13 AR ATN1 ATXN1 ATXN2 ATXN7 BECN1
6 endocrine/exocrine gland MP:0005379 10.11 AR ATN1 ATXN2 BECN1 CACNA1A HTT
7 nervous system MP:0003631 10.1 AR ATN1 ATXN1 ATXN2 ATXN3 ATXN7
8 integument MP:0010771 10.02 AR ATN1 BECN1 CACNA1A HTT PRKN
9 no phenotypic analysis MP:0003012 9.76 ATN1 CACNA1A HSPB1 HTR1A HTT PRKN
10 normal MP:0002873 9.61 AR ATN1 BECN1 CACNA1A HSPB1 HTT
11 reproductive system MP:0005389 9.32 AR ATN1 ATXN2 ATXN7 BECN1 CACNA1A

Drugs & Therapeutics for Machado-Joseph Disease

Drugs for Machado-Joseph Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 44)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mexiletine Approved, Investigational Phase 4 31828-71-4 4178
2 Anti-Arrhythmia Agents Phase 4
3 Sodium Channel Blockers Phase 4
4 Diuretics, Potassium Sparing Phase 4
5 Thyrotropin-Releasing Hormone Phase 4
6 Hormone Antagonists Phase 4
7 Nootropic Agents Phase 4
8 Hormones Phase 4
9 TA 0910 Phase 4
10
Lithium carbonate Approved Phase 2, Phase 3 554-13-2
11
Riluzole Approved, Investigational Phase 3 1744-22-5 5070
12
Glutamic acid Approved, Nutraceutical Phase 3 56-86-0 33032
13 Central Nervous System Depressants Phase 2, Phase 3
14 Tranquilizing Agents Phase 2, Phase 3
15 Psychotropic Drugs Phase 2, Phase 3
16 Antimanic Agents Phase 2, Phase 3
17 Antidepressive Agents Phase 2, Phase 3
18 Neurotransmitter Agents Phase 3
19 Anticonvulsants Phase 3
20 Neuroprotective Agents Phase 3
21 Protective Agents Phase 3
22 Excitatory Amino Acid Antagonists Phase 3
23 Excitatory Amino Acids Phase 3
24
Varenicline Approved, Investigational Phase 2 249296-44-4 5310966
25
Menthol Approved Phase 2 2216-51-5 16666
26
Calcium Approved, Nutraceutical Phase 2 7440-70-2 271
27 Nicotinic Agonists Phase 2
28 Cholinergic Agents Phase 2
29 Immunoglobulin G Phase 2
30 Antibodies Phase 2
31 Immunoglobulins Phase 2
32 Immunologic Factors Phase 2
33 Rho(D) Immune Globulin Phase 2
34 Immunoglobulins, Intravenous Phase 2
35 gamma-Globulins Phase 2
36 Calcium, Dietary Phase 2
37 Pharmaceutical Solutions Phase 1
38
4-Aminopyridine Approved 504-24-5 1727
39
tannic acid Approved 1401-55-4
40
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
41
Dopamine Approved 51-61-6, 62-31-7 681
42 Potassium Channel Blockers
43 Dopamine agonists
44 Omega 3 Fatty Acid

Interventional clinical trials:

(show top 50) (show all 55)
# Name Status NCT ID Phase Drugs
1 Mexiletine for the Treatment of Muscle Cramps in ALS Completed NCT01811355 Phase 4 Mexiletine;Placebo
2 Multicenter, Randomized, Double-blind, Placebo-controlled, Phase IV Clinical Trial to Evaluate and Compare the Safety and Efficacy of C-Trelin OD Tab 5mg(Taltirelin Hydrate) in Patients With Ataxia Induced by Spinocerebellar Degeneration Recruiting NCT04107740 Phase 4 C-Trelin OD Tab(5mg Taltirelin Hydrate);Placebo
3 Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3 Completed NCT01096082 Phase 2, Phase 3 Lithium Carbonate;Placebo
4 Efficacy of Riluzole in Hereditary Cerebellar Ataxia: a Randomized Double-blind Placebo-controlled Trial. Completed NCT01104649 Phase 2, Phase 3 riluzole;Placebo comparator
5 A Phase III, Long-Term, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Subjects With Spinocerebellar Ataxia. Recruiting NCT03701399 Phase 3 troriluzole;Placebos
6 Multicenter, Randomized, Double Blind, Placebo Controlled Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 Recruiting NCT03347344 Phase 3 Riluzole;Placebo
7 An Open Pilot Trial of BHV-4157 in Adult Subjects With Cerebellar Ataxia Active, not recruiting NCT03408080 Phase 3 BHV-4157
8 A Phase IIb/III, Randomized, Double-blind, Placebo-controlled Trial of BHV-4157 in Adult Subjects With Spinocerebellar Ataxia Active, not recruiting NCT02960893 Phase 2, Phase 3 BHV-4157;Placebo Comparator
9 A Clinical Research on the Safety/Efficacy of Umbilical Cord Mesenchymal Stem Cells Therapy for Patients With Spinocerebellar Ataxia Unknown status NCT03378414 Phase 2
10 A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study to Evaluate the Safety and Efficacy of Stemchymal® Infusion for the Treatment of Polyglutamine Spinocerebellar Ataxia Unknown status NCT02540655 Phase 2
11 Phase I/II Study of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia Unknown status NCT01360164 Phase 1, Phase 2
12 The Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cells Transplantation in Hereditary Cerebellar Ataxia Patients Unknown status NCT01489267 Phase 2
13 The Influence of Deep Repetitive Transcranial Magnetic Stimulation (TMS) on Cerebellar Signs in Patients With Spinocerebellar Ataxia Type 3 (SCA3 - Machado Joseph Disease) Completed NCT02039206 Phase 2
14 A Pilot, Randomized, Double-blind, Placebo-controlled Phase I Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3 Completed NCT00992771 Phase 2 varenicline;placebo
15 A Single-Center, Randomized, Double-Blind, Parallel-Group, Dose-Controlled Study, to Assess Safety, Tolerability and Efficacy of Intravenous Cabaletta® in Patients With Machado-Joseph Disease Completed NCT02147886 Phase 2 Cabaletta for IV infusion once weekly during 24 weeks;Cabaletta for IV infusion once weekly during 24 weeks
16 Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia Completed NCT01350440 Phase 2
17 Randomized, Placebo-controlled Trial to Test Safety, Tolerability and Efficacy of Lithium Carbonate in Spinocerebellar Ataxia 2 Completed NCT00998634 Phase 2 LITHIUM CARBONATE
18 Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia Completed NCT00202397 Phase 2 Riluzole
19 Effect of Nilotinib in Cerebellar Ataxia Patients Active, not recruiting NCT03932669 Phase 2 Nilotinib
20 Phenylbutyrate in SCA3: a Double-blind, Placebo-controlled Study to Determine Safety and Efficacy of Sodium Phenylbutyrate in Patients With SCA3 Withdrawn NCT01096095 Phase 2 Placebo;Sodium Phenylbutyrate
21 An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias Unknown status NCT02287064 Phase 1 Intravenous Immune Globulin (IVIG)
22 Pilot Study of Tolerability of Lithium Therapy in Patients With Spinocerebellar Ataxia Type I (SCA1) Completed NCT00683943 Phase 1 Lithium Carbonate
23 Machado-Joseph Disease in Israel: Clinical Phenotype and Genotype of a Jew Yemenite Subpopulation Unknown status NCT02175290
24 Prospective Study of Individuals at Risk for Spinocerebellar Ataxia Type 1, Type 2, Type 3, Type 6 and Type 7 (SCA1, SCA2, SCA3, SCA6, SCA7) Unknown status NCT01037777
25 Slowing Down Disease Progression in Premanifest SCA: a Piloting Interventional Exergame Trial Unknown status NCT02867969
26 Weight in Lower Limbs Improves Gait Ataxia Of in Machado-Joseph Disease Patients: A Randomized Crossover Trial Completed NCT02906046
27 Dysmetria in Motor Function in SCA: Mechanisms and Rehabilitation Completed NCT02488031
28 Therapeutic Effect of Dalfampridine on Gait Incoordination in Spinocerebellar Ataxias- A Randomized, Double-blinded, Placebo-controlled, Crossover Clinical Trial Completed NCT01811706 Dalfampridine;Placebo
29 Rehabilitative Trial With Cerebello-Spinal tDCS for the Treatment of Neurodegenerative Ataxia Completed NCT03120013
30 Integrative Medicine and Tai-chi in Clinical Status of Spinocerebellar Ataxia Completed NCT03687190 conventional medicine
31 Utility Of Home Based Gait Monitoring, Performance Scores And Functional Visual Assessment In Spinocerebellar Ataxias (SCA) Completed NCT00654251
32 Characterization of the Parkinsonism and Other Non-ataxia Spectrum and Striatal Dopaminergic Degeneration in Spinocerebellar Ataxia Type 6 Completed NCT01934998
33 Pathogenic Mechanism of Spinocerebellar Ataxia Type 10 (SCA10) Completed NCT00004306
34 Neuromuscular Electrical Stimulation on Median Nerve Facilitates Low Motor Cortex Excitability in Human With Spinocerebellar Ataxia Completed NCT02103075
35 Coordination Training With Complete Body Video Games in Children and Adults With Degenerative Ataxias Completed NCT02874911
36 Preliminary Study of the Scale To Assess Ataxia and Neurologic Dysfunction (STAND) Completed NCT02179333
37 Effects of Aerobic Exercise on Degenerative Cerebellar Disease Completed NCT03745248
38 The Effect of Whole Body Vibration Training on Neuromuscular Property in Individuals With Ataxia Completed NCT01983631
39 Transcranial Magnetic Stimulation (TMS) in Spino-Cerebellar Ataxia Completed NCT01975909
40 Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias Completed NCT01488461
41 The Investigation of the Pre-movement Facilitation of Agonist-antagonist Muscles and the Effect of the Feedforward Rehabilitation in Individuals With Hypermetria Completed NCT01983670
42 Translating Molecular Pathology Into a Therapeutic Strategy in SCA38, a Newly Identified Form of Spinocerebellar Ataxia Completed NCT03109626
43 Identification of Biomarkers in Patients With Autosomal Dominant Cerebellar Ataxia Completed NCT01470729
44 Identification of Biomarkers in Spinocerebellar Ataxia 3 Recruiting NCT03885167
45 Clinical Trial Readiness for SCA1 and SCA3 Recruiting NCT03487367
46 Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) to Study Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias (SCA) Recruiting NCT01060371
47 Derivation of Induced Pluripotent Stem Cells From Somatic Cells Donated by Patients With Neurological Diseases for the Study of the Pathogenesis of the Disorders and Development of Novel Therapies Recruiting NCT00874783
48 Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxias: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase Recruiting NCT04153110
49 Coordination of Rare Diseases at Sanford Recruiting NCT01793168
50 Hong Kong Spinocerebellar Ataxias Registry Recruiting NCT03336008

Search NIH Clinical Center for Machado-Joseph Disease

Cochrane evidence based reviews: machado-joseph disease

Genetic Tests for Machado-Joseph Disease

Genetic tests related to Machado-Joseph Disease:

# Genetic test Affiliating Genes
1 Azorean Disease 29 ATXN3

Anatomical Context for Machado-Joseph Disease

MalaCards organs/tissues related to Machado-Joseph Disease:

40
Eye, Tongue, Brain, Cerebellum, Spinal Cord, Testes, Cortex

Publications for Machado-Joseph Disease

Articles related to Machado-Joseph Disease:

(show top 50) (show all 1411)
# Title Authors PMID Year
1
CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. 61 24 56 6
7874163 1994
2
Proteotoxic stress increases nuclear localization of ataxin-3. 54 61 24 56
19843543 2010
3
High level expression of expanded full-length ataxin-3 in vitro causes cell death and formation of intranuclear inclusions in neuronal cells. 54 61 24 56
10369861 1999
4
Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. 54 61 24 56
8619527 1996
5
Evidence for inter-generational instability in the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. 54 61 24 56
8528200 1995
6
Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. 61 24 56
22113611 2011
7
Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease. 61 24 56
18385100 2008
8
Chronic pain in Machado-Joseph disease: a frequent and disabling symptom. 61 24 56
18071041 2007
9
Survival estimates for patients with Machado-Joseph disease (SCA3). 61 24 56
17894834 2007
10
Ribosomal frameshifting on MJD-1 transcripts with long CAG tracts. 61 24 56
16087686 2005
11
Founder haplotype for Machado-Joseph disease in the Indian population: novel insights from history and polymorphism studies. 61 24 56
15824265 2005
12
Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort. 61 24 56
15747371 2005
13
Autonomic dysfunction in Machado-Joseph disease. 61 24 56
15824264 2005
14
Cognitive impairments in Machado-Joseph disease. 61 24 56
15534186 2004
15
Haplotype study in Dutch SCA3 and SCA6 families: evidence for common founder mutations. 61 24 56
15026782 2004
16
Intermediate CAG repeat lengths (53,54) for MJD/SCA3 are associated with an abnormal phenotype. 61 24 56
11409435 2001
17
Ancestral origins of the Machado-Joseph disease mutation: a worldwide haplotype study. 61 24 56
11133357 2001
18
Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. 61 24 56
9635424 1998
19
Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. 61 24 56
8931575 1996
20
Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. 61 24 56
8640226 1996
21
Non-Mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph disease: the mutant allele is preferentially transmitted in male meiosis. 61 24 56
8644735 1996
22
Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus. 61 24 56
7573040 1995
23
Spinocerebellar ataxia type 1 and Machado-Joseph disease: incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia. 61 24 56
7668288 1995
24
Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorena Portuguese family. 61 24 56
7189034 1980
25
Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3? 54 61 56
20308049 2010
26
Reversibility of symptoms in a conditional mouse model of spinocerebellar ataxia type 3. 54 61 56
19666958 2009
27
Segregation distortion of wild-type alleles at the Machado-Joseph disease locus: a study in normal families from the Azores islands (Portugal). 54 61 56
18286225 2008
28
Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3. 24 56
15477548 2004
29
Prevalence and ethnic differences of autosomal-dominant cerebellar ataxia in Singapore. 24 56
12485197 2002
30
Dementia and delirium in 4 patients with Machado-Joseph disease. 54 61 56
12433269 2002
31
Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. 54 61 56
11939898 2002
32
Expanded CAG repeats in spinocerebellar ataxia (SCA1) segregate with distinct haplotypes in South african families. 54 61 56
9225982 1997
33
Non-Mendelian transmission at the Machado-Joseph disease locus in normal females: preferential transmission of alleles with smaller CAG repeats. 54 61 56
9132496 1997
34
Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease. 61 56
26373603 2015
35
Chinese homozygous Machado-Joseph disease (MJD)/SCA3: a case report. 61 56
25566755 2015
36
EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. 61 6
24418350 2014
37
High frequency of Machado-Joseph disease identified in southeastern Chinese kindreds with spinocerebellar ataxia. 54 61 24
20334689 2010
38
CK2-dependent phosphorylation determines cellular localization and stability of ataxin-3. 54 61 24
19542537 2009
39
Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history? 61 56
19329990 2009
40
Motor nerve hyperexcitability and muscle cramps in Machado-Joseph disease. 61 56
19139316 2009
41
Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3. 54 61 24
19036964 2008
42
Muscle excitability abnormalities in Machado-Joseph disease. 61 56
18413477 2008
43
Machado-Joseph disease enhances genetic fitness: a comparison between affected and unaffected women and between MJD and the general population. 61 56
17683516 2008
44
Mechanisms of ataxin-3 misfolding and fibril formation: kinetic analysis of a disease-associated polyglutamine protein. 54 61 24
17362987 2007
45
Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families. 61 56
17805477 2007
46
Proteolytic cleavage of polyglutamine-expanded ataxin-3 is critical for aggregation and sequestration of non-expanded ataxin-3. 61 56
16407371 2006
47
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition. 54 61 24
16020535 2005
48
Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism. 54 61 24
15808507 2005
49
A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration. 54 61 24
15537899 2004
50
Was the ataxia of Pierre Marie Machado-Joseph disease?: A reappraisal based on the last autopsy case from la Salpêtrière Hospital. 61 56
15148161 2004

Variations for Machado-Joseph Disease

ClinVar genetic disease variations for Machado-Joseph Disease:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ATXN3 NM_004993.5(ATXN3):c.892_894CAG(8_36) (p.Gln298_Gln305=)NT expansion Pathogenic,risk factor 3551 rs193922928 14:92537355-92537357 14:92071011-92071013
2 ATXN3 NM_004993.5(ATXN3):c.886_888CAG(60_86) (p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)NT expansion Pathogenic 209995 rs1555397179 14:92537382-92537384 14:92071038-92071040
3 ATXN3 NM_004993.6(ATXN3):c.916G>C (p.Gly306Arg)SNV Benign/Likely benign 128515 rs12895357 14:92537354-92537354 14:92071010-92071010
4 ATXN3 NM_004993.5(ATXN3):c.886_888CAG(12_44) (p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)NT expansion Benign 209994 rs1555397179 14:92537382-92537384 14:92071038-92071040

Expression for Machado-Joseph Disease

Search GEO for disease gene expression data for Machado-Joseph Disease.

Pathways for Machado-Joseph Disease

Pathways related to Machado-Joseph Disease according to KEGG:

36
# Name Kegg Source Accession
1 Protein processing in endoplasmic reticulum hsa04141

Pathways related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.56 VCP USP2 SNCA RPS27A PRKN BECN1
2
Show member pathways
13.15 HTT HSPB1 ATXN7 ATXN3 ATXN2 ATXN1
3
Show member pathways
12.37 SNCA SLC6A3 PRKN HSPB1 ATXN7 ATXN3
4
Show member pathways
12.33 VCP USP2 RPS27A PRKN BECN1 ATXN7
5 12.27 SNCA RPS27A PRKN HTT HTR1A ATXN1
6 11.93 VCP PRKN ATXN3L ATXN3
7
Show member pathways
11.65 VCP HSPB1 ATXN3
8 11.55 SNCA SLC6A3 PRKN ATXN2
9 11.05 SNCA SLC6A3 PRKN
10 10.1 VCP RPS27A PRKN ATXN3L ATXN3

GO Terms for Machado-Joseph Disease

Cellular components related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 10.22 VCP SNCA RPS27A PRKN HTT HSPB1
2 nucleus GO:0005634 10.2 VCP USP2 SNCA RPS27A PRKN HTT
3 protein-containing complex GO:0032991 9.85 VCP SNCA PRKN HTT BECN1 AR
4 cytoplasm GO:0005737 9.58 VCP USP2 SNCA SLC6A3 RPS27A PRKN
5 nuclear matrix GO:0016363 9.56 ATXN7 ATXN3 ATXN1 ATN1
6 perinuclear region of cytoplasm GO:0048471 9.56 VCP USP2 SNCA PRKN HTT CHERP
7 nuclear inclusion body GO:0042405 9.33 ATXN3L ATXN3 ATXN1

Biological processes related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.87 SNCA HTR1A CACNA1A ATXN3
2 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043161 9.8 VCP PRKN ATXN3L ATXN3
3 negative regulation of transcription by RNA polymerase II GO:0000122 9.8 USP2 SNCA RPS27A PRKN ATXN1 ATN1
4 macroautophagy GO:0016236 9.76 VCP PRKN BECN1
5 cellular response to heat GO:0034605 9.72 VCP ATXN3L ATXN3
6 ubiquitin-dependent protein catabolic process GO:0006511 9.72 VCP USP2 PRKN ATXN3L ATXN3
7 error-free translesion synthesis GO:0070987 9.62 VCP RPS27A
8 synaptic transmission, dopaminergic GO:0001963 9.61 SNCA PRKN
9 ERAD pathway GO:0036503 9.61 VCP PRKN
10 protein destabilization GO:0031648 9.61 SNCA PRKN HTT
11 dopamine metabolic process GO:0042417 9.6 SNCA PRKN
12 exploration behavior GO:0035640 9.59 HTR1A ATXN3L
13 protein quality control for misfolded or incompletely synthesized proteins GO:0006515 9.58 ATXN3L ATXN3
14 dopamine biosynthetic process GO:0042416 9.56 SNCA SLC6A3
15 cellular response to misfolded protein GO:0071218 9.54 ATXN3L ATXN3
16 positive regulation of autophagy of mitochondrion GO:1903599 9.52 PRKN HTT
17 monoubiquitinated protein deubiquitination GO:0035520 9.51 ATXN3L ATXN3
18 aggresome assembly GO:0070842 9.48 VCP PRKN
19 mitophagy GO:0000423 9.46 PRKN BECN1
20 regulation of cell-substrate adhesion GO:0010810 9.4 ATXN3L ATXN3
21 response to iron(II) ion GO:0010040 9.37 SNCA BECN1
22 regulation of dopamine metabolic process GO:0042053 9.33 SLC6A3 PRKN HTR1A
23 protein deubiquitination GO:0016579 9.28 VCP USP2 RPS27A PRKN BECN1 ATXN7
24 dopamine uptake involved in synaptic transmission GO:0051583 9.13 SNCA SLC6A3 PRKN

Molecular functions related to Machado-Joseph Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.91 VCP USP2 SNCA SLC6A3 RPS27A PRKN
2 identical protein binding GO:0042802 9.7 VCP USP2 SNCA PRKN HTT HSPB1
3 thiol-dependent ubiquitinyl hydrolase activity GO:0036459 9.58 USP2 ATXN3L ATXN3
4 thiol-dependent ubiquitin-specific protease activity GO:0004843 9.5 USP2 ATXN3L ATXN3
5 ubiquitin-specific protease binding GO:1990381 9.37 VCP PRKN
6 phospholipase binding GO:0043274 9.26 SNCA PRKN
7 ubiquitin protein ligase binding GO:0031625 9.17 VCP USP2 RPS27A PRKN BECN1 ATXN3L

Sources for Machado-Joseph Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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