MCID: NRD008
MIFTS: 40

Neurodegeneration with Brain Iron Accumulation 3

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

Aliases & Classifications for Neurodegeneration with Brain Iron Accumulation 3

MalaCards integrated aliases for Neurodegeneration with Brain Iron Accumulation 3:

Name: Neurodegeneration with Brain Iron Accumulation 3 54 12 24 25 71 13 14
Neuroferritinopathy 12 23 50 24 25 56 71 29 42 69
Hereditary Ferritinopathy 12 23 24 25 56
Ferritin-Related Neurodegeneration 12 50 25 56
Nbia3 12 24 25 71
Adult Basal Ganglia Disease 12 56
Neuroferritinopathy; Basal Ganglia Disease, Adult-Onset 12
Basal Ganglia Disease, Adult-Onset 25
Basal Ganglia Disease Adult-Onset 50
Adult-Onset Basal Ganglia Disease 71

Characteristics:

Orphanet epidemiological data:

56
neuroferritinopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult; Age of death: elderly;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
variable phenotype
onset 13 to 63 years of age


HPO:

32
neurodegeneration with brain iron accumulation 3:
Onset and clinical course phenotypic variability progressive
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Based on current data, penetrance is 100% [chinnery et al 2007]...

Classifications:



Summaries for Neurodegeneration with Brain Iron Accumulation 3

NIH Rare Diseases : 50 neuroferritinopathy is a movement disorder caused by the gradual accumulation of iron in the basal ganglia of the brain. people with neuroferritinopathy have progressive problems with movement that begin at about age 40. these movement problems can include involuntary jerking motions (chorea), rhythmic shaking (tremor), difficulty coordinating movements (ataxia), or uncontrolled tensing of muscles (dystonia). symptoms of the disorder may be more prominent on one side of the body. affected individuals may also have difficulty swallowing (dysphagia) and speaking (dysarthria). intelligence is generally unaffected, but some individuals develop a gradual decline in thinking and reasoning abilities (dementia). personality changes such as reduced inhibitions and difficulty controlling emotions may also occur as the disorder progresses. neuroferritinopathy is caused by mutations in the ftl gene. it is inherited in an autosomal dominant fashion. last updated: 9/24/2013

MalaCards based summary : Neurodegeneration with Brain Iron Accumulation 3, also known as neuroferritinopathy, is related to neurodegeneration with brain iron accumulation and sjogren's syndrome, and has symptoms including optic atrophy, dysphagia and dystonia. An important gene associated with Neurodegeneration with Brain Iron Accumulation 3 is FTL (Ferritin Light Chain). The drugs Deferiprone and Iron have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and cerebellum.

UniProtKB/Swiss-Prot : 71 Neurodegeneration with brain iron accumulation 3: A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild non-progressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.

Genetics Home Reference : 25 Neuroferritinopathy is a disorder in which iron gradually accumulates in the brain. Certain brain regions that help control movement (basal ganglia) are particularly affected. People with neuroferritinopathy have progressive problems with movement that begin at about age 40. These movement problems can include involuntary jerking motions (chorea), rhythmic shaking (tremor), difficulty coordinating movements (ataxia), or uncontrolled tensing of muscles (dystonia). Symptoms of the disorder may be more apparent on one side of the body than on the other. Affected individuals may also have difficulty swallowing (dysphagia) and speaking (dysarthria).

OMIM : 54
Neurodegeneration with brain iron accumulation is a genetically heterogeneous disorder characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia. Age at onset, cognitive involvement, and mode of inheritance is variable (review by Gregory et al., 2009). (606159)

Disease Ontology : 12 A neurodegeneration with brain iron accumulation that has material basis in autosomal dominant inheritance of mutation in the FTL gene on chromosome 19q13.33.

GeneReviews: NBK1141

Related Diseases for Neurodegeneration with Brain Iron Accumulation 3

Diseases in the Neurodegeneration with Brain Iron Accumulation family:

Neurodegeneration with Brain Iron Accumulation 6 Neurodegeneration with Brain Iron Accumulation 4
Neurodegeneration with Brain Iron Accumulation 3 Neurodegeneration with Brain Iron Accumulation 1
Neurodegeneration with Brain Iron Accumulation 2b Neurodegeneration with Brain Iron Accumulation 5

Diseases related to Neurodegeneration with Brain Iron Accumulation 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
id Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 10.8
2 sjogren's syndrome 10.2 FTL JPH3
3 ganglioneuroma 10.1 FTL PANK2
4 autosomal recessive early-onset parksinson disease 23 10.0 PANK2 PLA2G6
5 kufor-rakeb syndrome 10.0 PANK2 PLA2G6
6 dystonia 10.0
7 epilepsy, familial temporal lobe, 4 9.9 JPH3 PANK2
8 pupil disease 9.9 PANK2 PLA2G6
9 basal ganglia disease 9.9
10 tremor 9.8
11 chondrodysplasia punctata, x-linked dominant 9.8 C19orf12 PANK2 PLA2G6
12 spastic paraplegia 43, autosomal recessive 9.7 C19orf12 PANK2 PLA2G6
13 ectodermal dysplasia 13, hair/tooth type 9.7 C19orf12 PANK2 PLA2G6
14 leukodystrophy, hypomyelinating, 2 9.6 FA2H JPH3 PANK2
15 behr syndrome 9.6 C19orf12 FA2H
16 glucose/galactose malabsorption 9.5 FA2H PANK2 PLA2G6
17 naegeli-franceschetti-jadassohn syndrome 9.3 C19orf12 DCAF17 PANK2 PLA2G6
18 scrapie 9.1 C19orf12 FA2H PANK2 PLA2G6
19 parkinson disease 14, autosomal recessive 8.8 C19orf12 FA2H FTL PANK2 PLA2G6
20 hereditary spastic paraplegia 3a 8.8 C19orf12 FA2H FTL PANK2 PLA2G6
21 corneal endothelial dystrophy, autosomal recessive 8.4 C19orf12 FA2H FTL JPH3 PANK2 PLA2G6
22 herpes simplex encephalitis 7 7.1 C19orf12 DCAF17 FA2H FGF14 FTL JPH3

Graphical network of the top 20 diseases related to Neurodegeneration with Brain Iron Accumulation 3:



Diseases related to Neurodegeneration with Brain Iron Accumulation 3

Symptoms & Phenotypes for Neurodegeneration with Brain Iron Accumulation 3

Symptoms via clinical synopsis from OMIM:

54

Abdomen- Gastroin testinal:
dysphagia

Head And Neck- Eyes:
blepharospasm

Skeletal- Hands:
micrographia
writer's cramp

Respiratory- Larynx:
laryngeal dystonia

Respiratory:
pharyngeal dystonia

Neurologic- Central Nervous System:
dysarthria
tremor
hyperreflexia
extensor plantar responses
choreoathetosis
more
Neurologic- Behavioral Psychiatric Manifestations:
emotional lability
disinhibition

Head And Neck- Face:
oromandibular dyskinesia
orolingual dyskinesia
orofacial dystonia
hypomimia

Head And Neck- Mouth:
palatal tremor

Laboratory- Abnormalities:
decreased serum ferritin


Clinical features from OMIM:

606159

Human phenotypes related to Neurodegeneration with Brain Iron Accumulation 3:

56 32 (show all 37)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic atrophy 56 32 frequent (33%) Frequent (79-30%) HP:0000648
2 dysphagia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002015
3 dystonia 56 32 frequent (33%) Frequent (79-30%) HP:0001332
4 chorea 56 32 hallmark (90%) Very frequent (99-80%) HP:0002072
5 ataxia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001251
6 spasticity 56 32 Very frequent (99-80%) HP:0001257
7 retinal degeneration 56 32 frequent (33%) Frequent (79-30%) HP:0000546
8 parkinsonism 56 32 occasional (7.5%) Occasional (29-5%) HP:0001300
9 bradykinesia 56 32 frequent (33%) Frequent (79-30%) HP:0002067
10 intellectual disability 56 32 occasional (7.5%) Occasional (29-5%) HP:0001249
11 constipation 56 32 occasional (7.5%) Occasional (29-5%) HP:0002019
12 dementia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000726
13 dysphonia 56 32 frequent (33%) Frequent (79-30%) HP:0001618
14 developmental regression 56 32 occasional (7.5%) Occasional (29-5%) HP:0002376
15 spastic diplegia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001264
16 hypotension 56 32 occasional (7.5%) Occasional (29-5%) HP:0002615
17 orofacial dyskinesia 56 32 frequent (33%) Frequent (79-30%) HP:0002310
18 gait disturbance 56 32 frequent (33%) Frequent (79-30%) HP:0001288
19 language impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0002463
20 abnormality of eye movement 56 32 occasional (7.5%) Occasional (29-5%) HP:0000496
21 behavioral abnormality 56 32 occasional (7.5%) Occasional (29-5%) HP:0000708
22 dysarthria 32 HP:0001260
23 blepharospasm 32 HP:0000643
24 tremor 32 HP:0001337
25 hyperreflexia 32 HP:0001347
26 choreoathetosis 32 HP:0001266
27 emotional lability 32 HP:0000712
28 rigidity 32 HP:0002063
29 neurodegeneration 32 HP:0002180
30 disinhibition 32 HP:0000734
31 anarthria 32 HP:0002425
32 mutism 32 HP:0002300
33 laryngeal dystonia 32 HP:0012049
34 writer's cramp 32 HP:0002356
35 babinski sign 32 HP:0003487
36 decreased serum ferritin 32 HP:0012343
37 cavitation of the basal ganglia 32 HP:0007007

UMLS symptoms related to Neurodegeneration with Brain Iron Accumulation 3:


cerebellar ataxia, muscle rigidity, tremor, bradykinesia, abnormality of extrapyramidal motor function

Drugs & Therapeutics for Neurodegeneration with Brain Iron Accumulation 3

Drugs for Neurodegeneration with Brain Iron Accumulation 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Deferiprone Approved Phase 3,Phase 2 30652-11-0 2972
2
Iron Approved Phase 3,Phase 2 7439-89-6 23925
3 Chelating Agents Phase 3,Phase 2
4 Iron Chelating Agents Phase 3,Phase 2
5 Pharmaceutical Solutions Phase 3,Phase 2
6 Micronutrients Phase 2
7 Trace Elements Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 A Two-arm Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN) Completed NCT01741532 Phase 3 Deferiprone oral solution;Placebo oral solution
2 Efficacy and Safety of the Iron Chelator Deferiprone in Parkinson's Disease Completed NCT00943748 Phase 2, Phase 3 deferiprone;placebo
3 Efficacy and Safety Study of Fosmetpantotenate (RE-024) in PKAN Patients Recruiting NCT03041116 Phase 3 fosmetpantotenate (RE-024);Placebo
4 Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration Active, not recruiting NCT02174848 Phase 3 Deferiprone oral solution;Deferiprone
5 Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA) Unknown status NCT00907283 Phase 2 Deferiprone

Search NIH Clinical Center for Neurodegeneration with Brain Iron Accumulation 3

Cochrane evidence based reviews: neuroferritinopathy

Genetic Tests for Neurodegeneration with Brain Iron Accumulation 3

Genetic tests related to Neurodegeneration with Brain Iron Accumulation 3:

id Genetic test Affiliating Genes
1 Neuroferritinopathy 29 24 FTL

Anatomical Context for Neurodegeneration with Brain Iron Accumulation 3

MalaCards organs/tissues related to Neurodegeneration with Brain Iron Accumulation 3:

39
Brain, Eye, Cerebellum

Publications for Neurodegeneration with Brain Iron Accumulation 3

Variations for Neurodegeneration with Brain Iron Accumulation 3

UniProtKB/Swiss-Prot genetic disease variations for Neurodegeneration with Brain Iron Accumulation 3:

71
id Symbol AA change Variation ID SNP ID
1 FTL p.Ala96Thr VAR_026633 rs104894685

ClinVar genetic disease variations for Neurodegeneration with Brain Iron Accumulation 3:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 FTL FTL, 1-BP INS, 460A insertion Pathogenic
2 FTL NM_000146.3(FTL): c.286G> A (p.Ala96Thr) single nucleotide variant Pathogenic rs104894685 GRCh37 Chromosome 19, 49469574: 49469574
3 FTL NM_000146.3(FTL): c.498_499dup (p.Phe167Serfs) duplication Pathogenic rs1114167274 GRCh37 Chromosome 19, 49469962: 49469963
4 FTL NM_000146.3(FTL): c.469_484dup16 (p.Leu162Argfs) duplication Pathogenic rs398124640 GRCh37 Chromosome 19, 49469933: 49469948
5 FTL NM_000146.3(FTL): c.458dupA (p.His153Glnfs) duplication Pathogenic rs587776840 GRCh37 Chromosome 19, 49469922: 49469922

Expression for Neurodegeneration with Brain Iron Accumulation 3

Search GEO for disease gene expression data for Neurodegeneration with Brain Iron Accumulation 3.

Pathways for Neurodegeneration with Brain Iron Accumulation 3

GO Terms for Neurodegeneration with Brain Iron Accumulation 3

Biological processes related to Neurodegeneration with Brain Iron Accumulation 3 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 memory GO:0007613 8.62 JPH3 PLA2G6

Sources for Neurodegeneration with Brain Iron Accumulation 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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