MCID: NRD007
MIFTS: 45

Neurodegeneration with Brain Iron Accumulation

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

Aliases & Classifications for Neurodegeneration with Brain Iron Accumulation

MalaCards integrated aliases for Neurodegeneration with Brain Iron Accumulation:

Name: Neurodegeneration with Brain Iron Accumulation 12 53 54 37 29 6 44 15
Nbia 12 24 53
Neurodegeneration with Brain Iron Accumulation Disorders 24
Neurodegeneration, with Brain Iron Accumulation 40

Classifications:



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Disease Ontology 12 DOID:0110734
ICD10 33 G23.0
MeSH 44 C538421
KEGG 37 H00833
UMLS 73 C2931845

Summaries for Neurodegeneration with Brain Iron Accumulation

NIH Rare Diseases : 53 Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia. Symptoms include progressive dystonia (a movement disorder resulting in muscular spasms, twisting, and repetitive movements) spasticity, parkinsonism (slurred or slow speech, stiffness of the muscles, slow movement, and visible tremors), inability to coordinate movements (ataxia), neuropsychiatric abnormalities (confusion, disorientation, seizures, stupor, dementia), and eye problems, such as optic atrophy or retinal degeneration. The age of onset ranges from infancy to late adulthood, and the rate of progression varies. Some subtypes have cognitive decline. Cerebellar atrophy is common in many cases. There are ten recognized types of NBIA, classified according to the altered gene that causes the disease. These genes include PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP and  DCAF17. Eight of the ten types of NBIA are inherited in an autosomal recessive manner. The type known as beta-propeller protein-associated neurodegeneration (BPAN), caused by mutations in the WDR45 gene, is inherited in an X-linked dominant manner. The neuroferritinopathy, caused by mutations in the FTL gene, is inherited in an autosomal dominant manner. There is no cure for NBIA. Treatment is symptomatic, and includes medication such as baclofen, trihexyphenidyl, botulinum toxin, and a procedure known as  deep brain stimulation to treat dystonia.  Levodopa and anticholinergic drugs may also bring some relief of parkinsonian symptoms. The NBIA Disorders Association has detailed information about NBIA.  

MalaCards based summary : Neurodegeneration with Brain Iron Accumulation, also known as nbia, is related to neurodegeneration with brain iron accumulation 2b and neurodegeneration with brain iron accumulation 4. An important gene associated with Neurodegeneration with Brain Iron Accumulation is C19orf12 (Chromosome 19 Open Reading Frame 12), and among its related pathways/superpathways are Pantothenate and CoA biosynthesis and Porphyrin and chlorophyll metabolism. The drugs Deferiprone and Iron have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and globus pallidus, and related phenotypes are retinopathy and optic atrophy

NINDS : 54 Neurodegeneration with brain iron accumulation (NBIA) is a rare, inherited, neurological movement disorder characterized by an abnormal accumulation of iron in the brain and progressive degeneration of the nervous system.  Symptoms, which vary greatly among patients and usually develop during childhood, may include dystonia (slow writhing, distorting muscle contractions of the limbs, face, or trunk), dysarthria (slurred or slow speech) choreoathetosis (involuntary, purposeless jerky muscle movements), muscle rigidity (uncontrolled tightness of the muscles), spasticity (sudden, involuntary muscle spasms), and/or ataxia (inability to coordinate movements), confusion, disorientation, seizures, stupor, and dementia.  Visual changes are also common, most often due to atrophy of the optic nerve (optic atrophy) or degeneration of the retinal layer in the back of the eye (retinal degeneration).  Cognitive decline occurs in some forms of NBIA; the majority of individuals with NBIA do not have cognitive impairment.  Several genes have been found that cause NBIA.

Disease Ontology : 12 A neurodegenerative disease characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia.

Wikipedia : 76 Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurological disorders in... more...

GeneReviews: NBK121988

Related Diseases for Neurodegeneration with Brain Iron Accumulation

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 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 2b 34.3 FA2H PANK2 PLA2G6
2 neurodegeneration with brain iron accumulation 4 34.1 C19orf12 PANK2 PLA2G6 WDR45
3 neurodegeneration with brain iron accumulation 5 33.7 C19orf12 COASY PANK2 PLA2G6 WDR45
4 neurodegeneration with brain iron accumulation 3 33.1 C19orf12 FA2H FTL PANK2 PLA2G6
5 neurodegeneration with brain iron accumulation 6 32.9 C19orf12 COASY PANK2 PLA2G6 VPS13A
6 kufor-rakeb syndrome 31.7 ATP13A2 PANK2 PLA2G6
7 neurodegeneration with brain iron accumulation 1 31.6 C19orf12 COASY FA2H PANK2 PLA2G6 SNCA
8 neurodegeneration with brain iron accumulation 2a 30.2 ATP13A2 C19orf12 COASY FA2H FTL PANK2
9 tremor 29.9 C19orf12 SNCA
10 dystonia 29.7 C19orf12 FA2H PANK2 PLA2G6
11 aceruloplasminemia 27.9 ATP13A2 FA2H FTL PANK2 PLA2G6 SNCA
12 neurodegeneration with brain iron accumulation 7 12.4
13 neurodegeneration with brain iron accumulation 8 12.4
14 coasy protein-associated neurodegeneration 12.0
15 mitochondrial membrane protein-associated neurodegeneration 11.7
16 karak syndrome 11.4
17 atypical pantothenate kinase-associated neurodegeneration 11.4
18 spastic paraplegia 35, autosomal recessive 11.3
19 striatonigral degeneration, infantile 11.1
20 juvenile-onset parkinson's disease 10.2 ATP13A2 PLA2G6
21 neuroaxonal dystrophy 10.1 PANK2 PLA2G6 SNCA
22 psychotic disorder 10.1
23 type i 10.1
24 early-onset parkinson's disease 10.1 ATP13A2 SNCA
25 movement disease 10.0 FTL PANK2 SNCA
26 choreatic disease 10.0 FTL VPS13A
27 spastic paraparesis 10.0 DDHD1 FA2H
28 amyotrophic lateral sclerosis 1 9.9
29 mannosidosis 9.9
30 lateral sclerosis 9.9
31 neuronitis 9.9
32 juvenile amyotrophic lateral sclerosis 9.9
33 spasticity 9.9
34 spastic paraplegia 73, autosomal dominant 9.9 ATP13A2 FA2H
35 3-methylglutaconic aciduria, type iii 9.9 C19orf12 FA2H SNCA
36 spastic paraplegia 76, autosomal recessive 9.9 ATP13A2 FA2H
37 leukodystrophy, hypomyelinating, 2 9.7 FA2H PANK2 VPS13A
38 parkinson disease 15, autosomal recessive early-onset 9.2 ATP13A2 C19orf12 PANK2 PLA2G6 SNCA
39 synucleinopathy 9.2 ATP13A2 SNCA SNCB
40 multiple system atrophy 1 9.1 SNCA SNCB
41 trehalase deficiency 9.0 ATP13A2 FA2H PANK2 PLA2G6 WDR45
42 dementia 8.9 ATP13A2 SNCA SNCB
43 hereditary spastic paraplegia 8.9 ATP13A2 C19orf12 DDHD1 FA2H PLA2G6

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



Diseases related to Neurodegeneration with Brain Iron Accumulation

Symptoms & Phenotypes for Neurodegeneration with Brain Iron Accumulation

Human phenotypes related to Neurodegeneration with Brain Iron Accumulation:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 retinopathy 32 frequent (33%) HP:0000488
2 optic atrophy 32 frequent (33%) HP:0000648
3 spasticity 32 frequent (33%) HP:0001257
4 dysarthria 32 frequent (33%) HP:0001260
5 cerebellar atrophy 32 frequent (33%) HP:0001272
6 dystonia 32 hallmark (90%) HP:0001332
7 rigidity 32 frequent (33%) HP:0002063
8 abnormality of extrapyramidal motor function 32 frequent (33%) HP:0002071
9 chorea 32 frequent (33%) HP:0002072
10 iron accumulation in brain 32 hallmark (90%) HP:0012675

Drugs & Therapeutics for Neurodegeneration with Brain Iron Accumulation

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

(show all 7)
# 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:


# Name Status NCT ID Phase Drugs
1 Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration Completed NCT02174848 Phase 3 Deferiprone oral solution;Deferiprone
2 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
3 Efficacy and Safety of the Iron Chelator Deferiprone in Parkinson's Disease Completed NCT00943748 Phase 2, Phase 3 deferiprone;placebo
4 Efficacy and Safety Study of Fosmetpantotenate (RE-024) in PKAN Patients Recruiting NCT03041116 Phase 3 fosmetpantotenate (RE-024);Placebo
5 Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA) Unknown status NCT00907283 Phase 2 Deferiprone
6 Brain Perfusion in Pantothenate Kinase-associated Neurodegeneration (PKAN) Completed NCT01838018
7 NBIAready: Online Collection of Natural History Patient-reported Outcome Measures Recruiting NCT02587858
8 Compassionate Use of Deferiprone in Patients With PKAN Available NCT02635841 Deferiprone
9 Imaging Neuromelanin and Iron in Dystonia/Parkinsonism Not yet recruiting NCT03572114

Search NIH Clinical Center for Neurodegeneration with Brain Iron Accumulation

Cochrane evidence based reviews: neurodegeneration with brain iron accumulation

Genetic Tests for Neurodegeneration with Brain Iron Accumulation

Genetic tests related to Neurodegeneration with Brain Iron Accumulation:

# Genetic test Affiliating Genes
1 Neurodegeneration with Brain Iron Accumulation 29

Anatomical Context for Neurodegeneration with Brain Iron Accumulation

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

41
Brain, Eye, Globus Pallidus

Publications for Neurodegeneration with Brain Iron Accumulation

Articles related to Neurodegeneration with Brain Iron Accumulation:

(show top 50) (show all 69)
# Title Authors Year
1
AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation? ( 29473051 )
2018
2
Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. ( 29395073 )
2018
3
Botulinum Toxin-A Injection in the Treatment of Spasticity in a Infantile-Onset Neurodegeneration With Brain Iron Accumulation: A Case Report. ( 29765892 )
2018
4
Neurodegeneration with brain iron accumulation. ( 29325618 )
2018
5
On the complexity of clinical and molecular bases of neurodegeneration with brain iron accumulation. ( 28542792 )
2017
6
A homozygous splice variant in AP4S1 mimicking neurodegeneration with brain iron accumulation. ( 28150420 )
2017
7
Clinical and Imaging Presentation of aA Patient with Beta-Propeller Protein-Associated Neurodegeneration, aA Rare and Sporadic form of Neurodegeneration with Brain Iron Accumulation (NBIA). ( 28643035 )
2017
8
Neurodegeneration with brain iron accumulation. ( 28987166 )
2017
9
Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation. ( 28818478 )
2017
10
Visual and ocular motor function in the atypical form of neurodegeneration with brain iron accumulation type I. ( 28487376 )
2017
11
Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories. ( 25870938 )
2016
12
Neurodegeneration with brain iron accumulation (NBIA) formerly Hallervorden- Spatz disease. ( 27728536 )
2016
13
Mitochondrial dysfunction and defects in lipid homeostasis as therapeutic targets in neurodegeneration with brain iron accumulation. ( 27141409 )
2016
14
Neurodegeneration with brain iron accumulation. ( 27487369 )
2016
15
Neurodegeneration with Brain Iron Accumulation. ( 26739693 )
2016
16
Severe early basal ganglia hypometabolism in neurodegeneration with brain iron accumulation. ( 26993314 )
2016
17
Neurodegeneration with brain iron accumulation presenting motor trick and impaired motor cortical plasticity. ( 26773698 )
2016
18
Neurodegeneration with brain iron accumulation: A case report. ( 29213449 )
2016
19
A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging. ( 27487380 )
2016
20
SCP2 mutations and neurodegeneration with brain iron accumulation. ( 26497993 )
2015
21
Aceruloplasminemia: neurodegeneration with brain iron accumulation (NBIA) associated with parkinsonism. ( 25413956 )
2015
22
Mitochondria: A crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases. ( 25668476 )
2015
23
Self-Mutilation in Neurodegeneration with Brain Iron Accumulation. ( 26120159 )
2015
24
Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation. ( 25592411 )
2015
25
Role of A^a8,F-FDG PET imaging in paediatric primary dystonia and dystonia arising from neurodegeneration with brain iron accumulation. ( 25646707 )
2015
26
Neurodegeneration with brain iron accumulation: diagnosis and management. ( 25614780 )
2015
27
C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation. ( 25962551 )
2015
28
Neurodegeneration with Brain Iron Accumulation: Genetic Diversity and Pathophysiological Mechanisms. ( 25973518 )
2015
29
Ophthalmic features of PLA2G6-related paediatric neurodegeneration with brain iron accumulation. ( 24522175 )
2014
30
Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. ( 24360804 )
2014
31
Efficacy and safety of deferiprone for the treatment of pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA): results from a four years follow-up. ( 24661465 )
2014
32
Proceedings of the third joint symposium on neuroacanthocytosis and neurodegeneration with brain iron accumulation: from benchside to bedside. ( 25621189 )
2014
33
Neurodegeneration with brain iron accumulation: an overview. ( 25657764 )
2014
34
Clinical features of neurodegeneration with brain iron accumulation due to a C19orf12 gene mutation. ( 23494994 )
2013
35
Psychotic Disorder in Neurodegeneration with Brain Iron Accumulation. ( 24047758 )
2013
36
Teaching NeuroImages: neurodegeneration with brain iron accumulation in aceruloplasminemia. ( 24218322 )
2013
37
PANK2 and C19orf12 mutations are common causes of neurodegeneration with brain iron accumulation. ( 23166001 )
2013
38
Pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN): review of two major neurodegeneration with brain iron accumulation (NBIA) phenotypes. ( 24209433 )
2013
39
Neurodegeneration with Brain Iron Accumulation on MRI: An Adult Case of I+-Mannosidosis. ( 23430902 )
2012
40
C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis. ( 22584950 )
2012
41
Neurodegeneration with brain iron accumulation. ( 22691760 )
2012
42
Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. ( 22743658 )
2012
43
C19orf12 and FA2H mutations are rare in Italian patients with neurodegeneration with brain iron accumulation. ( 22704260 )
2012
44
Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. ( 21981780 )
2011
45
Coexistence of TDP-43 and tau pathology in neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome). ( 21276079 )
2011
46
Neurodegeneration with brain iron accumulation. ( 21496576 )
2011
47
Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA). ( 20853438 )
2010
48
ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. ( 20310007 )
2010
49
Clinicopathological variability in neurodegeneration with brain iron accumulation. ( 20405671 )
2010
50
Iron accumulation in syndromes of neurodegeneration with brain iron accumulation 1 and 2: causative or consequential? ( 19147629 )
2009

Variations for Neurodegeneration with Brain Iron Accumulation

ClinVar genetic disease variations for Neurodegeneration with Brain Iron Accumulation:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PLA2G6 NM_001199562.2(PLA2G6): c.1749delC (p.Ser583Argfs) deletion Likely pathogenic rs730882214 GRCh38 Chromosome 22, 38115650: 38115650
2 PLA2G6 NM_001199562.2(PLA2G6): c.1749delC (p.Ser583Argfs) deletion Likely pathogenic rs730882214 GRCh37 Chromosome 22, 38511657: 38511657

Expression for Neurodegeneration with Brain Iron Accumulation

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

Pathways for Neurodegeneration with Brain Iron Accumulation

Pathways related to Neurodegeneration with Brain Iron Accumulation according to KEGG:

37
# Name Kegg Source Accession
1 Pantothenate and CoA biosynthesis hsa00770
2 Porphyrin and chlorophyll metabolism hsa00860
3 Fc epsilon RI signaling pathway hsa04664
4 Serotonergic synapse hsa04726
5 Long-term depression hsa04730
6 Mineral absorption hsa04978

Pathways related to Neurodegeneration with Brain Iron Accumulation according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.9 COASY PANK2

GO Terms for Neurodegeneration with Brain Iron Accumulation

Cellular components related to Neurodegeneration with Brain Iron Accumulation according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.63 C19orf12 COASY PANK2 PLA2G6 SNCA SNCB
2 cytosol GO:0005829 9.32 C19orf12 COASY DDHD1 FTL PANK2 PLA2G6
3 inclusion body GO:0016234 8.96 SNCA SNCB

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

# Name GO ID Score Top Affiliating Genes
1 autophagy GO:0006914 9.43 C19orf12 VPS13A WDR45
2 cellular iron ion homeostasis GO:0006879 9.4 ATP13A2 FTL
3 negative regulation of neuron death GO:1901215 9.37 ATP13A2 SNCA
4 synapse organization GO:0050808 9.32 SNCA SNCB
5 dopamine metabolic process GO:0042417 9.16 SNCA SNCB
6 coenzyme A biosynthetic process GO:0015937 8.96 COASY PANK2
7 coenzyme biosynthetic process GO:0009108 8.62 COASY PANK2

Molecular functions related to Neurodegeneration with Brain Iron Accumulation according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol-3,5-bisphosphate binding GO:0080025 8.96 ATP13A2 WDR45
2 cuprous ion binding GO:1903136 8.62 SNCA SNCB

Sources for Neurodegeneration with Brain Iron Accumulation

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
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45 MESH via Orphanet
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