MCID: NRD008
MIFTS: 41

Neurodegeneration with Brain Iron Accumulation 3

Categories: Genetic diseases, Rare diseases, Eye diseases, Neuronal diseases, Metabolic 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 53 12 24 71 13 14
Neuroferritinopathy 53 12 23 49 24 55 71 36 28 41 69
Ferritin-Related Neurodegeneration 12 49 24 55
Hereditary Ferritinopathy 12 23 24 55
Nbia3 53 12 24 71
Basal Ganglia Disease, Adult-Onset 53 24
Adult Basal Ganglia Disease 12 55
Neuroferritinopathy; Basal Ganglia Disease, Adult-Onset 12
Basal Ganglia Disease Adult-Onset 49
Adult-Onset Basal Ganglia Disease 71

Characteristics:

Orphanet epidemiological data:

55
neuroferritinopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult; Age of death: elderly;

OMIM:

53
Inheritance:
autosomal dominant

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


HPO:

31
neurodegeneration with brain iron accumulation 3:
Onset and clinical course phenotypic variability progressive
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Penetrance is 100% [chinnery et al 2007]...

Classifications:



Summaries for Neurodegeneration with Brain Iron Accumulation 3

NIH Rare Diseases : 49 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 dystonia, and has symptoms including ataxia, constipation and dystonia. An important gene associated with Neurodegeneration with Brain Iron Accumulation 3 is FTL (Ferritin Light Chain). Affiliated tissues include brain, eye and cerebellum.

OMIM : 53 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)

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 : 24 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).

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

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

(show all 19)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 30.0 C19orf12 FA2H FTL PANK2 PLA2G6
2 dystonia 29.0 C19orf12 FA2H PANK2 PLA2G6
3 choreatic disease 10.1 FTL JPH3
4 juvenile-onset parkinson disease 10.0 PANK2 PLA2G6
5 kufor-rakeb syndrome 9.9 PANK2 PLA2G6
6 basal ganglia disease 9.9
7 tremor 9.9
8 movement disease 9.9 FTL PANK2
9 neuroaxonal dystrophy 9.9 PANK2 PLA2G6
10 neurodegeneration with brain iron accumulation 5 9.8 C19orf12 PANK2 PLA2G6
11 neurodegeneration with brain iron accumulation 4 9.8 C19orf12 PANK2 PLA2G6
12 parkinson disease 15, autosomal recessive early-onset 9.7 C19orf12 PANK2 PLA2G6
13 leukodystrophy, hypomyelinating, 2 9.6 FA2H JPH3 PANK2
14 3-methylglutaconic aciduria, type iii 9.6 C19orf12 FA2H
15 neurodegeneration with brain iron accumulation 2b 9.6 FA2H PANK2 PLA2G6
16 neurodegeneration with brain iron accumulation 6 9.4 C19orf12 DCAF17 PANK2 PLA2G6
17 aceruloplasminemia 9.3 FA2H FTL PANK2 PLA2G6
18 neurodegeneration with brain iron accumulation 2a 9.1 C19orf12 FA2H FTL PANK2 PLA2G6
19 neurodegeneration with brain iron accumulation 1 9.0 C19orf12 FA2H JPH3 PANK2 PLA2G6

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:

53
Neurologic Central Nervous System:
tremor
cerebellar ataxia
bradykinesia
dysarthria
hyperreflexia
more
Abdomen Gastroin testinal:
dysphagia

Skeletal Hands:
writer's cramp
micrographia

Laboratory Abnormalities:
decreased serum ferritin

Head And Neck Mouth:
palatal tremor

Neurologic Behavioral Psychiatric Manifestations:
emotional lability
disinhibition

Head And Neck Eyes:
blepharospasm

Respiratory Larynx:
laryngeal dystonia

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

Respiratory:
pharyngeal dystonia


Clinical features from OMIM:

606159

Human phenotypes related to Neurodegeneration with Brain Iron Accumulation 3:

55 31 (show all 38)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001251
2 constipation 55 31 occasional (7.5%) Occasional (29-5%) HP:0002019
3 dystonia 55 31 frequent (33%) Frequent (79-30%) HP:0001332
4 bradykinesia 55 31 frequent (33%) Frequent (79-30%) HP:0002067
5 abnormality of eye movement 55 31 occasional (7.5%) Occasional (29-5%) HP:0000496
6 intellectual disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001249
7 spasticity 55 31 Very frequent (99-80%) HP:0001257
8 gait disturbance 55 31 frequent (33%) Frequent (79-30%) HP:0001288
9 dysphonia 55 31 frequent (33%) Frequent (79-30%) HP:0001618
10 dysphagia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002015
11 chorea 55 31 hallmark (90%) Very frequent (99-80%) HP:0002072
12 developmental regression 55 31 occasional (7.5%) Occasional (29-5%) HP:0002376
13 hypotension 55 31 occasional (7.5%) Occasional (29-5%) HP:0002615
14 behavioral abnormality 55 31 occasional (7.5%) Occasional (29-5%) HP:0000708
15 optic atrophy 55 31 frequent (33%) Frequent (79-30%) HP:0000648
16 dementia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000726
17 spastic diplegia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001264
18 parkinsonism 55 31 occasional (7.5%) Occasional (29-5%) HP:0001300
19 language impairment 55 31 occasional (7.5%) Occasional (29-5%) HP:0002463
20 retinal degeneration 55 31 frequent (33%) Frequent (79-30%) HP:0000546
21 orofacial dyskinesia 55 31 frequent (33%) Frequent (79-30%) HP:0002310
22 tremor 31 HP:0001337
23 emotional lability 31 HP:0000712
24 dysarthria 31 HP:0001260
25 hyperreflexia 31 HP:0001347
26 babinski sign 31 HP:0003487
27 rigidity 31 HP:0002063
28 neurodegeneration 31 HP:0002180
29 blepharospasm 31 HP:0000643
30 choreoathetosis 31 HP:0001266
31 disinhibition 31 HP:0000734
32 anarthria 31 HP:0002425
33 mutism 31 HP:0002300
34 hypomimic face 31 HP:0000338
35 writer's cramp 31 HP:0002356
36 laryngeal dystonia 31 HP:0012049
37 decreased serum ferritin 31 HP:0012343
38 cavitation of the basal ganglia 31 HP:0007007

UMLS symptoms related to Neurodegeneration with Brain Iron Accumulation 3:


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

Drugs & Therapeutics for Neurodegeneration with Brain Iron Accumulation 3

Search Clinical Trials , 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:

# Genetic test Affiliating Genes
1 Neuroferritinopathy 28 FTL

Anatomical Context for Neurodegeneration with Brain Iron Accumulation 3

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

38
Brain, Eye, Cerebellum

Publications for Neurodegeneration with Brain Iron Accumulation 3

Articles related to Neurodegeneration with Brain Iron Accumulation 3:

(show all 37)
# Title Authors Year
1
Cortical pencil lining in neuroferritinopathy: A diagnostic clue. ( 25832658 )
2015
2
Neuroferritinopathy: From ferritin structure modification to pathogenetic mechanism. ( 25772441 )
2015
3
Behavioral characterization of mouse models of neuroferritinopathy. ( 25689865 )
2015
4
A novel neuroferritinopathy mouse model (FTL 498InsTC) shows progressive brain iron dysregulation, morphological signs of early neurodegeneration and motor coordination deficits. ( 25447222 )
2014
5
Neuroferritinopathy: iron in the brain. ( 24949097 )
2014
6
A novel FTL mutation responsible for neuroferritinopathy with asymmetric clinical features and brain anomalies. ( 24907184 )
2014
7
A novel ferritin light chain mutation in neuroferritinopathy with an atypical presentation. ( 24825732 )
2014
8
Early neuropsychiatry features in neuroferritinopathy. ( 23436236 )
2013
9
Case 193: Neuroferritinopathy--a brain iron accumulation and neurodegenerative disorder. ( 23610097 )
2013
10
Neuroferritinopathy. ( 24209436 )
2013
11
Neuroferritinopathy. ( 22818529 )
2012
12
MRI findings in neuroferritinopathy. ( 21808735 )
2012
13
Neuroferritinopathy: update on clinical features and pathogenesis. ( 22515742 )
2012
14
Progressive brain iron accumulation in neuroferritinopathy measured by the thalamic T2* relaxation rate. ( 22499840 )
2012
15
Neuroferritinopathy: a new inborn error of iron metabolism. ( 22278127 )
2012
16
Teaching NeuroImages: neuroferritinopathy. ( 22042801 )
2011
17
The man who could not walk backward: an unusual presentation of neuroferritinopathy. ( 21294155 )
2011
18
Oxidative stress and cell death in cells expressing L-ferritin variants causing neuroferritinopathy. ( 19781644 )
2010
19
A novel FTL insertion causing neuroferritinopathy. ( 20065344 )
2010
20
Dramatic response of facial stereotype/tic to tetrabenazine in the first reported cases of neuroferritinopathy in the United States. ( 20818611 )
2010
21
Clinical features and natural history of neuroferritinopathy caused by the 458dupA FTL mutation. ( 18854324 )
2009
22
A novel ferritin light chain gene mutation in a Japanese family with neuroferritinopathy: description of clinical features and implications for genotype-phenotype correlations. ( 19117339 )
2009
23
Neuroferritinopathy in a Japanese family with a duplication in the ferritin light chain gene. ( 18413574 )
2008
24
Preliminary observation of elevated levels of nanocrystalline iron oxide in the basal ganglia of neuroferritinopathy patients. ( 17097860 )
2007
25
Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. ( 17142829 )
2007
26
p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy. ( 16825958 )
2006
27
Characterization of the l-ferritin variant 460InsA responsible of a hereditary ferritinopathy disorder. ( 16822677 )
2006
28
Neuroferritinopathy. ( 17101456 )
2006
29
Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin mutation. ( 15737889 )
2005
30
Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement. ( 16116125 )
2005
31
Hereditary ferritinopathy: a novel mutation, its cellular pathology, and pathogenetic insights. ( 15835264 )
2005
32
Spectrum of movement disorders in neuroferritinopathy. ( 15390132 )
2005
33
Adult-onset generalized dystonia due to a mutation in the neuroferritinopathy gene. ( 15390032 )
2005
34
Neuroferritinopathy in a French family with late onset dominant dystonia. ( 12746423 )
2003
35
Neuroferritinopathy: a window on the role of iron in neurodegeneration. ( 12547246 )
2002
36
Palatal tremor and cognitive decline in neuroferritinopathy. ( 12082064 )
2002
37
Neuroferritinopathy ( 20301320 )
1993

Variations for Neurodegeneration with Brain Iron Accumulation 3

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

71
# 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
# 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:

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

Sources for Neurodegeneration with Brain Iron Accumulation 3

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70 UMLS via Orphanet
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