NIID
MCID: NRN008
MIFTS: 45

Neuronal Intranuclear Inclusion Disease (NIID)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neuronal Intranuclear Inclusion Disease

MalaCards integrated aliases for Neuronal Intranuclear Inclusion Disease:

Name: Neuronal Intranuclear Inclusion Disease 56 52 58 54 6 39 71
Niid 56 52
Neuronal Intranuclear Hyaline Inclusion Disease 52

Characteristics:

Orphanet epidemiological data:

58
neuronal intranuclear inclusion disease
Age of onset: All ages;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
variable manifestations
adult-onset
patients may present with limb muscle weakness and gait abnormalities or cognitive impairment


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM 56 603472
MESH via Orphanet 44 C537395
ICD10 via Orphanet 33 G31.0
UMLS via Orphanet 72 C1863843
Orphanet 58 ORPHA2289
UMLS 71 C1863843

Summaries for Neuronal Intranuclear Inclusion Disease

NIH Rare Diseases : 52 Neuronal intranuclear inclusion disease (NIID) is a slowly progressive, neurodegenerative disease . NIID may affect any part of the nervous system (central, peripheral , and/or autonomic ), as well as various organs . Signs and symptoms may begin anywhere from infancy to late adulthood, and can vary from person to person. In most cases, the disease begins in childhood. Symptoms of NIID worsen over time and may include dementia , limb weakness, cerebellar ataxia , dystonia , parkinsonism , seizures , and autonomic dysfunction . Therefore, people with NIID may have impairment of balance, movement, cognition, communication, behavior, and the ability to function independently. In general, limb weakness and ataxia are more common in children with NIID, while dementia is more common in people diagnosed in adulthood. The features of NIID result from the presence of eosinophilic intranuclear inclusions inside neurons and glial cells (abnormal masses of substances in the nuclei of cells of the nervous system). The reason this occurs is not known. Both sporadic and familial cases have been reported. However, specific genes known to cause NIID have not yet been found. Currently there is no treatment that cures or slows the progression of NIID, but medications that help control symptoms may improve quality of life. While the disease is ultimately fatal, life expectancy can range significantly, from one year to several decades after the diagnosis.

MalaCards based summary : Neuronal Intranuclear Inclusion Disease, also known as niid, is related to dentatorubral-pallidoluysian atrophy and movement disease. An important gene associated with Neuronal Intranuclear Inclusion Disease is NOTCH2NLC (Notch 2 N-Terminal Like C), and among its related pathways/superpathways are Neuroscience and Synaptic vesicle cycle. Affiliated tissues include brain, skin and skeletal muscle, and related phenotypes are ataxia and dysarthria

OMIM : 56 Neuronal intranuclear inclusion disease (NIID) is an autosomal dominant, slowly progressive neurodegenerative disorder characterized by a wide range of clinical manifestations, including pyramidal and extrapyramidal symptoms, cerebellar ataxia, cognitive decline and dementia, peripheral neuropathy, and autonomic dysfunction. The age at onset varies, but most individuals present as adults between about 30 and 70 years of age. Pathologic investigation shows eosinophilic intranuclear inclusions in almost all cell types, including neurons, skin cells, fibroblasts, and skeletal muscle. Brain imaging shows a characteristic leukoencephalopathy with high intensity signals in the corticomedullary junction on diffusion-weighted imaging (DWI), as well as white matter abnormalities in subcortical and brainstem regions. Skin biopsy combined with brain imaging is useful for diagnosis (summary by Sone et al., 2016). The phenotype in some cases is suggestive of Parkinson disease (see 168600) and/or Alzheimer disease (see 104300), consistent with an evolving phenotypic spectrum of adult-onset NIID (summary by Tian et al., 2019). (603472)

Related Diseases for Neuronal Intranuclear Inclusion Disease

Diseases related to Neuronal Intranuclear Inclusion Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 94)
# Related Disease Score Top Affiliating Genes
1 dentatorubral-pallidoluysian atrophy 30.2 PML ATXN3 ATXN1
2 movement disease 29.9 SNCA MAPT ATXN3
3 aceruloplasminemia 29.6 SNCA MAPT DNM1 ATXN3 ATXN1
4 multiple system atrophy 1 29.0 SNCA RPS27A MAPT ATXN3 ATXN1
5 dementia 29.0 SNCA RPS27A MAPT ATXN3 ATXN1
6 machado-joseph disease 28.9 SNCA RPS27A HSP90AA1 ATXN3 ATXN1
7 huntington disease 28.7 SNCA RPS27A MAPT ATXN3 ATXN1
8 amyotrophic lateral sclerosis 1 27.4 STXBP1 SNCA RPS27A MAPT HSP90AA1 ATXN3
9 ataxia and polyneuropathy, adult-onset 10.6
10 tremor 10.4
11 neuropathy 10.3
12 fmr1 disorders 10.3
13 yemenite deaf-blind hypopigmentation syndrome 10.3
14 night blindness 10.3
15 pathologic nystagmus 10.3
16 pure autonomic failure 10.3
17 rare neurodegenerative disease 10.3
18 primary cerebellar degeneration 10.3 ATXN3 ATXN1
19 leptospirosis 10.2
20 human immunodeficiency virus infectious disease 10.2
21 fragile x-associated tremor/ataxia syndrome 10.2
22 status epilepticus 10.2
23 dystonia 10.2
24 dysphagia 10.2
25 encephalopathy 10.2
26 atherosclerosis susceptibility 10.2
27 kearns-sayre syndrome 10.2
28 abnormal pupillary function 10.2
29 constipation 10.2
30 motor neuron disease 10.2
31 poliomyelitis 10.2
32 internuclear ophthalmoplegia 10.2
33 nervous system disease 10.2
34 seizure disorder 10.2
35 spinocerebellar degeneration 10.2
36 spinal and bulbar muscular atrophy, x-linked 1 10.1 HSP90AA1 ATXN3 ATXN1
37 alzheimer disease 10.0
38 atrial standstill 1 10.0
39 systemic lupus erythematosus 10.0
40 migraine with or without aura 1 10.0
41 oculopharyngodistal myopathy 1 10.0
42 myasthenia gravis 10.0
43 wilson disease 10.0
44 fragile x tremor/ataxia syndrome 10.0
45 human immunodeficiency virus type 1 10.0
46 oculopharyngeal myopathy with leukoencephalopathy 1 10.0
47 aspiration pneumonia 10.0
48 sexual disorder 10.0
49 ptosis 10.0
50 amnestic disorder 10.0

Graphical network of the top 20 diseases related to Neuronal Intranuclear Inclusion Disease:



Diseases related to Neuronal Intranuclear Inclusion Disease

Symptoms & Phenotypes for Neuronal Intranuclear Inclusion Disease

Human phenotypes related to Neuronal Intranuclear Inclusion Disease:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
3 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
4 seizures 58 31 frequent (33%) Frequent (79-30%) HP:0001250
5 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
6 eeg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0002353
7 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
8 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
9 behavioral abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0000708
10 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
11 abnormal form of the vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0003312
12 ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000602
13 dementia 58 31 frequent (33%) Frequent (79-30%) HP:0000726
14 spina bifida occulta 58 31 frequent (33%) Frequent (79-30%) HP:0003298
15 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
16 abnormality of the pharynx 58 31 occasional (7.5%) Occasional (29-5%) HP:0000600
17 neurological speech impairment 58 Very frequent (99-80%)
18 abnormality of movement 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
ataxia
dysarthria
tremor
rigidity
neurodegeneration
more
Neurologic Peripheral Nervous System:
hyporeflexia
distal sensory impairment
slowed nerve conduction velocities
axonal neuropathy
sensorimotor peripheral neuropathy
more
Head And Neck Eyes:
miosis
visual abnormalities

Muscle Soft Tissue:
distal muscle atrophy
distal muscle weakness (may affect bulbar regions)

Abdomen Gastrointestinal:
constipation
fecal incontinence

Genitourinary Bladder:
urinary incontinence
bladder dysfunction

Neurologic Behavioral Psychiatric Manifestations:
apathy
executive dysfunction
behavioral changes

Laboratory Abnormalities:
eosinophilic intranuclear inclusions in various cells, including adipocytes, muscle cells, schwann cells, sweat gland cells, and vascular smooth muscle cells
inclusions stain positively for ubiquitin and p62 (sqstm1)

Clinical features from OMIM:

603472

MGI Mouse Phenotypes related to Neuronal Intranuclear Inclusion Disease:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 APBA1 ATXN1 ATXN3 DNM1 HDAC4 HSP90AA1
2 no phenotypic analysis MP:0003012 9.1 APBA1 DNM1 MAPT PML SNCA STXBP1

Drugs & Therapeutics for Neuronal Intranuclear Inclusion Disease

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Structural and Functional Changes in Neuronal Intranuclear Inclusion Disease: A Pioneer Multi-modal 7T MRI Observational Study. Recruiting NCT04055857
2 A Multicenter Prospective,Randomized and Controlled Pilot Study on the Diagnostic Strategy of So-called Two-step Method in Patients With FUO Enrolling by invitation NCT02035670

Search NIH Clinical Center for Neuronal Intranuclear Inclusion Disease

Genetic Tests for Neuronal Intranuclear Inclusion Disease

Anatomical Context for Neuronal Intranuclear Inclusion Disease

MalaCards organs/tissues related to Neuronal Intranuclear Inclusion Disease:

40
Brain, Skin, Skeletal Muscle, Cerebellum, Smooth Muscle, Adipocyte, Testes

Publications for Neuronal Intranuclear Inclusion Disease

Articles related to Neuronal Intranuclear Inclusion Disease:

(show top 50) (show all 130)
# Title Authors PMID Year
1
Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease. 61 56 6
31332380 2019
2
Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. 61 56 6
31332381 2019
3
Expansion of Human-Specific GGC Repeat in Neuronal Intranuclear Inclusion Disease-Related Disorders. 61 56 6
31178126 2019
4
Familial neuronal intranuclear inclusion disease with ubiquitin positive inclusions. 54 61 56
9804114 1998
5
Long-read sequencing identified repeat expansions in the 5'UTR of the NOTCH2NLC gene from Chinese patients with neuronal intranuclear inclusion disease. 61 56
31413119 2019
6
An Autopsy Case of Familial Neuronal Intranuclear Inclusion Disease with Dementia and Neuropathy. 61 56
30101925 2018
7
Case of a 78-year-old woman with a neuronal intranuclear inclusion disease. 61 56
29265760 2017
8
Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. 61 56
27797808 2016
9
Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion Disease. 61 56
27523009 2016
10
Neuronal intranuclear inclusion disease presenting with resting tremor. 61 56
24987362 2014
11
Hereditary neuronal intranuclear inclusion disease with autonomic failure and cerebellar degeneration. 61 56
12164731 2002
12
Neuronal intranuclear inclusion disease in identical twins. 61 56
6331275 1984
13
Case of adult-onset neuronal intranuclear hyaline inclusion disease with negative electroretinogram. 56
28332008 2017
14
Simultaneous skin-nerve-muscle biopsy and abnormal mitochondrial inclusions in intranuclear hyaline inclusion body disease. 56
27823834 2017
15
Neuronal intranuclear inclusion disease: two cases of dopa-responsive juvenile parkinsonism with drug-induced dyskinesia. 61 52
20629123 2010
16
Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy. 56
16301479 2005
17
Adult-onset neuronal intranuclear hyaline inclusion disease is not rare in older adults. 52
27018283 2016
18
Neuronal intranuclear inclusion disease and juvenile parkinsonism. 54 61
11009211 2000
19
Interrelated Pathogenesis? Neuronal Intranuclear Inclusion Disease Combining With Hemiplegic Migraine. 61
31701545 2020
20
Heterozygous GGC repeat expansion of NOTCH2NLC in a patient with neuronal intranuclear inclusion disease and progressive retinal dystrophy. 61
32039647 2020
21
Recent progress in neuronal intranuclear inclusion disease: a review of the literature. 61
31897935 2020
22
Diagnostic indicators for adult-onset neuronal intranuclear inclusion disease. 61
31661069 2020
23
Adult-onset neuronal intranuclear inclusion disease presenting with typical MRI changes. 61
31749292 2019
24
A case of recurrent vomiting: extending the spectrum of neuronal intranuclear inclusion disease. 61
31267307 2019
25
GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy. 61
31433517 2019
26
The Envelope Residues E152/156/158 of Zika Virus Influence the Early Stages of Virus Infection in Human Cells. 61
31731738 2019
27
Identifying patients with neuronal intranuclear inclusion disease in Singapore using characteristic diffusion-weighted MR images. 61
31292692 2019
28
Neuronal Intranuclear Inclusion Disease: Longitudinal Case Report of Motor and Nonmotor Symptoms. 61
31304825 2019
29
Neuronal Intranuclear Inclusion Disease: A Rare Etiology for Rapidly Progressive Dementia. 61
31094708 2019
30
[Two cases of adult-onset neuronal intranuclear inclusion disease diagnosed by skin biopsy]. 61
31461821 2019
31
[Sporadic adult-onset neuronal intranuclear inclusion disease: a case report]. 61
31365986 2019
32
Reader response: Neuronal intranuclear inclusion disease showing intranuclear inclusions in renal biopsy 12 years earlier. 61
31451592 2019
33
Author response: Neuronal intranuclear inclusion disease showing intranuclear inclusions in renal biopsy 12 years earlier. 61
31451593 2019
34
Reader response: Neuronal intranuclear inclusion disease showing intranuclear inclusions in renal biopsy 12 years earlier. 61
31451594 2019
35
Editors' note: Neuronal intranuclear inclusion disease showing intranuclear inclusions in renal biopsy 12 years earlier. 61
31451591 2019
36
Teaching NeuroImages: The zigzag edging sign of adult-onset neuronal intranuclear inclusion disease. 61
31451595 2019
37
Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review. 61
31331269 2019
38
[Neuronal intranuclear inclusion disease with prolonged impaired consciousness and status epilepticus: a case report]. 61
31243248 2019
39
A multimodal imaging features of the brain in adult-onset neuronal intranuclear inclusion disease. 61
30726521 2019
40
Refining the Spectrum of Neuronal Intranuclear Inclusion Disease: A Case Report. 61
31150092 2019
41
Neuronal intranuclear inclusion disease showing blepharoptosis and positive serum anti-acetylcholine receptor antibody without myasthenia gravis. 61
30925359 2019
42
Teaching NeuroImages: The zigzag edging sign of adult-onset neuronal intranuclear inclusion disease. 61
31061218 2019
43
Correction to: A multimodal imaging features of the brain in adult-onset neuronal intranuclear inclusion disease. 61
30806862 2019
44
Non-convulsive status epilepticus associated with neuronal intranuclear inclusion disease: A case report and literature review. 61
30891404 2019
45
A long time radiological follow-up of neuronal intranuclear inclusion disease: Two case reports. 61
30544465 2018
46
Neuronal intranuclear inclusion disease showing intranuclear inclusions in renal biopsy 12 years earlier. 61
30282768 2018
47
Two cases of sporadic adult-onset neuronal intranuclear inclusion disease preceded by urinary disturbance for many years. 61
30031993 2018
48
A Case of Juvenile Onset Neuronal Intranuclear Inclusion Disease With a Negative Antemortem Skin Biopsy. 61
28853324 2018
49
MR Imaging Features of Adult-Onset Neuronal Intranuclear Inclusion Disease May Be Indistinguishable from Fragile X-Associated Tremor/Ataxia Syndrome. 61
30072371 2018
50
[An adult onset sporadic neuronal intranuclear inclusion disease case reminiscent with Fisher syndrome]. 61
30068807 2018

Variations for Neuronal Intranuclear Inclusion Disease

ClinVar genetic disease variations for Neuronal Intranuclear Inclusion Disease:

6 ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NOTCH2NLC NOTCH2NLC, (GGC)n REPEAT EXPANSIONNT expansion Pathogenic 691867

Expression for Neuronal Intranuclear Inclusion Disease

Search GEO for disease gene expression data for Neuronal Intranuclear Inclusion Disease.

Pathways for Neuronal Intranuclear Inclusion Disease

Pathways related to Neuronal Intranuclear Inclusion Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.63 STXBP1 SNCA RPS27A NSF MAPT ATXN1
2
Show member pathways
11.61 STXBP1 NSF DNM1
3 10.77 SUMO1 HSP90AA1
4 10.66 SUMO1 HSP90AA1 HDAC4
5 10.34 RPS27A ATXN3
6 10.2 SUMO1 HDAC4

GO Terms for Neuronal Intranuclear Inclusion Disease

Cellular components related to Neuronal Intranuclear Inclusion Disease according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.07 SUMO1 STXBP1 SNCA RPS27A PML MAPT
2 cytoplasm GO:0005737 9.97 SUMO1 STXBP1 SNCA RPS27A PML NSF
3 synapse GO:0045202 9.85 SUMO1 SNCA DNM1 ATXN3 APBA1
4 protein-containing complex GO:0032991 9.83 STXBP1 SNCA HSP90AA1 HDAC4 DNM1
5 axon GO:0030424 9.8 STXBP1 SNCA MAPT DNM1
6 synaptic vesicle GO:0008021 9.65 SNCA DNM1 APBA1
7 nuclear matrix GO:0016363 9.58 PML ATXN3 ATXN1
8 nucleolus GO:0005730 9.43 SUMO1 RPS27A PML ATXN3 ATXN1 ABT1
9 cytosol GO:0005829 9.4 SUMO1 STXBP1 SNCA RPS27A PML NSF
10 nuclear inclusion body GO:0042405 9.37 ATXN3 ATXN1
11 presynaptic active zone membrane GO:0048787 9.32 STXBP1 APBA1

Biological processes related to Neuronal Intranuclear Inclusion Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of exocytosis GO:0045921 9.43 STXBP1 SNCA
2 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.43 SNCA PML MAPT
3 positive regulation of receptor recycling GO:0001921 9.4 SNCA NSF
4 synaptic vesicle priming GO:0016082 9.37 STXBP1 SNCA
5 supramolecular fiber organization GO:0097435 9.32 SNCA MAPT
6 SNARE complex assembly GO:0035493 9.16 STXBP1 SNCA
7 PML body organization GO:0030578 8.96 SUMO1 PML
8 cellular response to heat GO:0034605 8.92 SUMO1 MAPT HSP90AA1 ATXN3

Molecular functions related to Neuronal Intranuclear Inclusion Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.16 SUMO1 STXBP1 SNCA RPS27A PML NSF
2 protein kinase binding GO:0019901 9.77 STXBP1 NSF MAPT HDAC4 DNM1
3 identical protein binding GO:0042802 9.7 STXBP1 SNCA MAPT HSP90AA1 HDAC4 DNM1
4 RNA binding GO:0003723 9.56 SUMO1 STXBP1 RPS27A MAPT HSP90AA1 DNM1
5 SNARE binding GO:0000149 9.5 STXBP1 SNCA NSF
6 syntaxin-1 binding GO:0017075 9.48 STXBP1 NSF
7 ATPase activity, coupled GO:0042623 9.46 NSF HSP90AA1
8 phospholipase binding GO:0043274 9.43 STXBP1 SNCA
9 protein tag GO:0031386 9.4 SUMO1 RPS27A
10 ubiquitin protein ligase binding GO:0031625 9.02 SUMO1 RPS27A PML HSP90AA1 ATXN3

Sources for Neuronal Intranuclear Inclusion 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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