MCID: NRD008
MIFTS: 38

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 57 12 25 75 13 15
Neuroferritinopathy 57 12 24 53 25 59 75 37 29 6 44 73
Ferritin-Related Neurodegeneration 12 53 25 59
Hereditary Ferritinopathy 12 24 25 59
Nbia3 57 12 25 75
Basal Ganglia Disease, Adult-Onset 57 25
Adult Basal Ganglia Disease 12 59
Neuroferritinopathy; Basal Ganglia Disease, Adult-Onset 12
Neurodegeneration, with Brain Iron Accumulation, Type 3 40
Basal Ganglia Disease Adult-Onset 53
Adult-Onset Basal Ganglia Disease 75

Characteristics:

Orphanet epidemiological data:

59
neuroferritinopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult; Age of death: elderly;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
progressive disorder
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:

24
Penetrance Penetrance is 100% [chinnery et al 2007]...

Classifications:



Summaries for Neurodegeneration with Brain Iron Accumulation 3

NIH Rare Diseases : 53 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.

MalaCards based summary : Neurodegeneration with Brain Iron Accumulation 3, also known as neuroferritinopathy, is related to movement disease and neurodegeneration with brain iron accumulation, and has symptoms including cerebellar ataxia, muscle rigidity and tremor. An important gene associated with Neurodegeneration with Brain Iron Accumulation 3 is FTL (Ferritin Light Chain). Affiliated tissues include brain, eye and cerebellum, and related phenotypes are abnormality of eye movement and intellectual disability

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.

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 : 57 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 : 75 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.

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 Neurodegeneration with Brain Iron Accumulation 7
Neurodegeneration with Brain Iron Accumulation 8

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

(show all 20)
# Related Disease Score Top Affiliating Genes
1 movement disease 29.9 FTL PANK2
2 neurodegeneration with brain iron accumulation 29.2 C19orf12 FA2H FTL PANK2 PLA2G6
3 dystonia 28.4 C19orf12 FA2H PANK2 PLA2G6
4 choreatic disease 10.2 FTL JPH3
5 kufor-rakeb syndrome 10.0 PANK2 PLA2G6
6 basal ganglia disease 9.9
7 tremor 9.9
8 neuroaxonal dystrophy 9.9 PANK2 PLA2G6
9 parkinson disease 15, autosomal recessive early-onset 9.7 C19orf12 PANK2 PLA2G6
10 3-methylglutaconic aciduria, type iii 9.6 C19orf12 FA2H
11 neurodegeneration with brain iron accumulation 4 9.6 C19orf12 PANK2 PLA2G6
12 neurodegeneration with brain iron accumulation 5 9.6 C19orf12 PANK2 PLA2G6
13 leukodystrophy, hypomyelinating, 2 9.4 FA2H JPH3 PANK2
14 neurodegeneration with brain iron accumulation 2b 9.4 FA2H PANK2 PLA2G6
15 hereditary spastic paraplegia 9.3 C19orf12 FA2H PLA2G6
16 neurodegeneration with brain iron accumulation 6 9.1 C19orf12 DCAF17 PANK2 PLA2G6
17 aceruloplasminemia 9.0 FA2H FTL PANK2 PLA2G6
18 trehalase deficiency 8.7 FA2H PANK2 PLA2G6
19 neurodegeneration with brain iron accumulation 2a 8.6 C19orf12 FA2H FTL PANK2 PLA2G6
20 neurodegeneration with brain iron accumulation 1 8.5 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:

57
Neurologic Behavioral Psychiatric Manifestations:
emotional lability
disinhibition

Abdomen Gastrointestinal:
dysphagia

Skeletal Hands:
writer's cramp
micrographia

Laboratory Abnormalities:
decreased serum ferritin

Head And Neck Mouth:
palatal tremor

Neurologic Central Nervous System:
dysarthria
tremor
hyperreflexia
dysphonia
rigidity
more
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:

59 32 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of eye movement 59 32 occasional (7.5%) Occasional (29-5%) HP:0000496
2 intellectual disability 59 32 occasional (7.5%) Occasional (29-5%) HP:0001249
3 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
4 spasticity 59 32 Very frequent (99-80%) HP:0001257
5 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
6 dysphonia 59 32 frequent (33%) Frequent (79-30%) HP:0001618
7 dysphagia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002015
8 constipation 59 32 occasional (7.5%) Occasional (29-5%) HP:0002019
9 chorea 59 32 hallmark (90%) Very frequent (99-80%) HP:0002072
10 developmental regression 59 32 occasional (7.5%) Occasional (29-5%) HP:0002376
11 hypotension 59 32 occasional (7.5%) Occasional (29-5%) HP:0002615
12 behavioral abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0000708
13 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
14 dystonia 59 32 frequent (33%) Frequent (79-30%) HP:0001332
15 dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000726
16 bradykinesia 59 32 frequent (33%) Frequent (79-30%) HP:0002067
17 spastic diplegia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001264
18 parkinsonism 59 32 occasional (7.5%) Occasional (29-5%) HP:0001300
19 language impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0002463
20 retinal degeneration 59 32 frequent (33%) Frequent (79-30%) HP:0000546
21 orofacial dyskinesia 59 32 frequent (33%) Frequent (79-30%) HP:0002310
22 emotional lability 32 HP:0000712
23 dysarthria 32 HP:0001260
24 tremor 32 HP:0001337
25 hyperreflexia 32 HP:0001347
26 abnormality of metabolism/homeostasis 32 HP:0001939
27 babinski sign 32 HP:0003487
28 rigidity 32 HP:0002063
29 neurodegeneration 32 HP:0002180
30 choreoathetosis 32 HP:0001266
31 blepharospasm 32 HP:0000643
32 writer's cramp 32 HP:0002356
33 disinhibition 32 HP:0000734
34 anarthria 32 HP:0002425
35 hypomimic face 32 HP:0000338
36 mutism 32 HP:0002300
37 laryngeal dystonia 32 HP:0012049
38 decreased serum ferritin 32 HP:0012343
39 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, cerebellar signs

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 29 FTL

Anatomical Context for Neurodegeneration with Brain Iron Accumulation 3

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

41
Brain, Eye, Cerebellum

Publications for Neurodegeneration with Brain Iron Accumulation 3

Articles related to Neurodegeneration with Brain Iron Accumulation 3:

# Title Authors Year
1
Abnormal iron metabolism in fibroblasts from a patient with the neurodegenerative disease hereditary ferritinopathy. ( 21067605 )
2010
2
p53-mediated apoptosis, neuroglobin overexpression, and globin deposits in a patient with hereditary ferritinopathy. ( 16825958 )
2006
3
Characterization of the l-ferritin variant 460InsA responsible of a hereditary ferritinopathy disorder. ( 16822677 )
2006
4
Hereditary ferritinopathy: a novel mutation, its cellular pathology, and pathogenetic insights. ( 15835264 )
2005

Variations for Neurodegeneration with Brain Iron Accumulation 3

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

75
# 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
(show top 50) (show all 65)
# Gene Variation Type Significance SNP ID Assembly Location
1 FTL NM_000146.3(FTL): c.498_499dup (p.Phe167Serfs) duplication Pathogenic rs1114167274 GRCh38 Chromosome 19, 48966705: 48966706
2 FTL NM_000146.3(FTL): c.469_484dup16 (p.Leu162Argfs) duplication Pathogenic rs398124640 GRCh37 Chromosome 19, 49469933: 49469948
3 FTL NM_000146.3(FTL): c.469_484dup16 (p.Leu162Argfs) duplication Pathogenic rs398124640 GRCh38 Chromosome 19, 48966676: 48966691
4 FTL FTL, 1-BP INS, 460A insertion Pathogenic
5 FTL NM_000146.3(FTL): c.286G> A (p.Ala96Thr) single nucleotide variant Pathogenic rs104894685 GRCh37 Chromosome 19, 49469574: 49469574
6 FTL NM_000146.3(FTL): c.286G> A (p.Ala96Thr) single nucleotide variant Pathogenic rs104894685 GRCh38 Chromosome 19, 48966317: 48966317
7 FTL NM_000146.3(FTL): c.498_499dup (p.Phe167Serfs) duplication Pathogenic rs1114167274 GRCh37 Chromosome 19, 49469962: 49469963
8 FTL NM_000146.3(FTL): c.458dupA (p.His153Glnfs) duplication Pathogenic rs587776840 GRCh37 Chromosome 19, 49469922: 49469922
9 FTL NM_000146.3(FTL): c.458dupA (p.His153Glnfs) duplication Pathogenic rs587776840 GRCh38 Chromosome 19, 48966665: 48966665
10 FTL NM_000146.3(FTL): c.169G> A (p.Glu57Lys) single nucleotide variant Uncertain significance rs201241191 GRCh38 Chromosome 19, 48965836: 48965836
11 FTL NM_000146.3(FTL): c.169G> A (p.Glu57Lys) single nucleotide variant Uncertain significance rs201241191 GRCh37 Chromosome 19, 49469093: 49469093
12 FTL; GYS1 NM_000146.3(FTL): c.163T> C (p.Leu55=) single nucleotide variant Benign rs2230267 GRCh38 Chromosome 19, 48965830: 48965830
13 FTL; GYS1 NM_000146.3(FTL): c.163T> C (p.Leu55=) single nucleotide variant Benign rs2230267 GRCh37 Chromosome 19, 49469087: 49469087
14 FTL NM_000146.3(FTL): c.*8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs373178636 GRCh37 Chromosome 19, 49470000: 49470000
15 FTL NM_000146.3(FTL): c.*8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs373178636 GRCh38 Chromosome 19, 48966743: 48966743
16 FTL NM_000146.3(FTL): c.-46C> A single nucleotide variant Uncertain significance rs768457741 GRCh38 Chromosome 19, 48965462: 48965462
17 FTL NM_000146.3(FTL): c.-46C> A single nucleotide variant Uncertain significance rs768457741 GRCh37 Chromosome 19, 49468719: 49468719
18 FTL; GYS1 NM_002103.4(GYS1): c.*659C> T single nucleotide variant Conflicting interpretations of pathogenicity rs367578611 GRCh37 Chromosome 19, 49471886: 49471886
19 FTL; GYS1 NM_002103.4(GYS1): c.*659C> T single nucleotide variant Conflicting interpretations of pathogenicity rs367578611 GRCh38 Chromosome 19, 48968629: 48968629
20 FTL; GYS1 NM_002103.4(GYS1): c.*450G> A single nucleotide variant Likely benign rs3745693 GRCh37 Chromosome 19, 49472095: 49472095
21 FTL; GYS1 NM_002103.4(GYS1): c.*450G> A single nucleotide variant Likely benign rs3745693 GRCh38 Chromosome 19, 48968838: 48968838
22 FTL; GYS1 NM_002103.4(GYS1): c.1848C> T (p.Ala616=) single nucleotide variant Conflicting interpretations of pathogenicity rs145789213 GRCh37 Chromosome 19, 49473074: 49473074
23 FTL; GYS1 NM_002103.4(GYS1): c.1848C> T (p.Ala616=) single nucleotide variant Conflicting interpretations of pathogenicity rs145789213 GRCh38 Chromosome 19, 48969817: 48969817
24 FTL; GYS1 NM_002103.4(GYS1): c.1615G> A (p.Glu539Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs561646250 GRCh37 Chromosome 19, 49474215: 49474215
25 FTL; GYS1 NM_002103.4(GYS1): c.1615G> A (p.Glu539Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs561646250 GRCh38 Chromosome 19, 48970958: 48970958
26 FTL; GYS1 NM_002103.4(GYS1): c.*841A> G single nucleotide variant Likely benign rs75797604 GRCh38 Chromosome 19, 48968447: 48968447
27 FTL; GYS1 NM_002103.4(GYS1): c.*841A> G single nucleotide variant Likely benign rs75797604 GRCh37 Chromosome 19, 49471704: 49471704
28 FTL; GYS1 NM_002103.4(GYS1): c.2207G> A (p.Arg736His) single nucleotide variant Conflicting interpretations of pathogenicity rs367919986 GRCh37 Chromosome 19, 49472552: 49472552
29 FTL; GYS1 NM_002103.4(GYS1): c.2207G> A (p.Arg736His) single nucleotide variant Conflicting interpretations of pathogenicity rs367919986 GRCh38 Chromosome 19, 48969295: 48969295
30 FTL; GYS1 NM_002103.4(GYS1): c.2013C> T (p.Asp671=) single nucleotide variant Conflicting interpretations of pathogenicity rs5452 GRCh37 Chromosome 19, 49472746: 49472746
31 FTL; GYS1 NM_002103.4(GYS1): c.2013C> T (p.Asp671=) single nucleotide variant Conflicting interpretations of pathogenicity rs5452 GRCh38 Chromosome 19, 48969489: 48969489
32 FTL; GYS1 NM_002103.4(GYS1): c.1926G> A (p.Val642=) single nucleotide variant Benign/Likely benign rs5451 GRCh37 Chromosome 19, 49472833: 49472833
33 FTL; GYS1 NM_002103.4(GYS1): c.1926G> A (p.Val642=) single nucleotide variant Benign/Likely benign rs5451 GRCh38 Chromosome 19, 48969576: 48969576
34 FTL NM_000146.3(FTL): c.522C> T (p.His174=) single nucleotide variant Likely benign rs73046709 GRCh38 Chromosome 19, 48966729: 48966729
35 FTL NM_000146.3(FTL): c.522C> T (p.His174=) single nucleotide variant Likely benign rs73046709 GRCh37 Chromosome 19, 49469986: 49469986
36 FTL NM_000146.3(FTL): c.*24C> T single nucleotide variant Likely benign rs368083362 GRCh38 Chromosome 19, 48966759: 48966759
37 FTL NM_000146.3(FTL): c.*24C> T single nucleotide variant Likely benign rs368083362 GRCh37 Chromosome 19, 49470016: 49470016
38 FTL; GYS1 NM_002103.4(GYS1): c.*725C> T single nucleotide variant Benign/Likely benign rs1042265 GRCh37 Chromosome 19, 49471820: 49471820
39 FTL; GYS1 NM_002103.4(GYS1): c.*725C> T single nucleotide variant Benign/Likely benign rs1042265 GRCh38 Chromosome 19, 48968563: 48968563
40 FTL; GYS1 NM_002103.4(GYS1): c.*370A> C single nucleotide variant Conflicting interpretations of pathogenicity rs185366453 GRCh37 Chromosome 19, 49472175: 49472175
41 FTL; GYS1 NM_002103.4(GYS1): c.*370A> C single nucleotide variant Conflicting interpretations of pathogenicity rs185366453 GRCh38 Chromosome 19, 48968918: 48968918
42 FTL; GYS1 NM_002103.4(GYS1): c.*301G> A single nucleotide variant Conflicting interpretations of pathogenicity rs147489255 GRCh37 Chromosome 19, 49472244: 49472244
43 FTL; GYS1 NM_002103.4(GYS1): c.*301G> A single nucleotide variant Conflicting interpretations of pathogenicity rs147489255 GRCh38 Chromosome 19, 48968987: 48968987
44 FTL NM_000146.3(FTL): c.-92T> C single nucleotide variant Uncertain significance rs886054563 GRCh38 Chromosome 19, 48965416: 48965416
45 FTL NM_000146.3(FTL): c.-92T> C single nucleotide variant Uncertain significance rs886054563 GRCh37 Chromosome 19, 49468673: 49468673
46 FTL NM_000146.3(FTL): c.73C> T (p.Leu25=) single nucleotide variant Likely benign rs201971200 GRCh38 Chromosome 19, 48965580: 48965580
47 FTL NM_000146.3(FTL): c.73C> T (p.Leu25=) single nucleotide variant Likely benign rs201971200 GRCh37 Chromosome 19, 49468837: 49468837
48 FTL NM_000146.3(FTL): c.*131A> T single nucleotide variant Uncertain significance rs374919004 GRCh38 Chromosome 19, 48966866: 48966866
49 FTL NM_000146.3(FTL): c.*131A> T single nucleotide variant Uncertain significance rs374919004 GRCh37 Chromosome 19, 49470123: 49470123
50 FTL; GYS1 NM_002103.4(GYS1): c.*1113_*1116delAGTG deletion Conflicting interpretations of pathogenicity rs148396922 GRCh38 Chromosome 19, 48968172: 48968175

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 8.96 JPH3 PLA2G6
2 regulation of synaptic plasticity GO:0048167 8.62 FGF14 JPH3

Sources for Neurodegeneration with Brain Iron Accumulation 3

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