NBIA
MCID: NRD007
MIFTS: 48

Neurodegeneration with Brain Iron Accumulation (NBIA)

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



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 4 and neurodegeneration with brain iron accumulation 5. An important gene associated with Neurodegeneration with Brain Iron Accumulation is CRAT (Carnitine O-Acetyltransferase), and among its related pathways/superpathways are Pantothenate and CoA biosynthesis and Porphyrin and chlorophyll metabolism. The drugs Iron and Deferiprone have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and globus pallidus, and related phenotypes are spasticity and dysarthria

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.

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.

Wikipedia : 76 Neurodegeneration with brain iron accumulation (NBIA) is a heterogenous group of inherited neurological... 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 48)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 4 34.7 C19orf12 PANK2 PLA2G6 WDR45
2 neurodegeneration with brain iron accumulation 5 34.6 C19orf12 COASY PANK2 PLA2G6 WDR45
3 neurodegeneration with brain iron accumulation 2b 34.5 FA2H PANK2 PLA2G6
4 neurodegeneration with brain iron accumulation 2a 34.5 FA2H PANK2 PLA2G6
5 neurodegeneration with brain iron accumulation 3 34.2 C19orf12 FA2H FTL PANK2 PLA2G6
6 neurodegeneration with brain iron accumulation 6 34.2 C19orf12 COASY PANK2 PLA2G6 VPS13A
7 neurodegeneration with brain iron accumulation 1 34.0 C19orf12 COASY FA2H PANK2 PLA2G6 SNCA
8 kufor-rakeb syndrome 32.0 ATP13A2 PANK2 PLA2G6
9 dystonia 29.9 C19orf12 FA2H FTL PANK2 PLA2G6 SLC39A14
10 aceruloplasminemia 29.8 ATP13A2 FA2H FTL PANK2 PLA2G6 SNCA
11 neurodegeneration with brain iron accumulation 7 12.8
12 neurodegeneration with brain iron accumulation 8 12.8
13 coasy protein-associated neurodegeneration 12.2
14 mitochondrial membrane protein-associated neurodegeneration 11.9
15 karak syndrome 11.5
16 spastic paraplegia 35, autosomal recessive 11.4
17 striatonigral degeneration, infantile 11.3
18 amyotrophic lateral sclerosis 1 10.2
19 dementia 10.2
20 lateral sclerosis 10.2
21 psychotic disorder 10.2
22 basal ganglia disease 10.1 CRAT FTL
23 juvenile-onset parkinson's disease 10.1 ATP13A2 PLA2G6
24 krabbe disease 10.1 PLA2G6 SNCA
25 choreatic disease 10.1 FTL VPS13A
26 neuroaxonal dystrophy 10.1 FA2H PANK2 PLA2G6
27 spinocerebellar ataxia, autosomal recessive 21 10.0 ATP13A2 FA2H
28 autism 10.0
29 frontotemporal dementia 10.0
30 mannosidosis 10.0
31 leukodystrophy 10.0
32 juvenile amyotrophic lateral sclerosis 10.0
33 frontotemporal dementia with parkinsonism-17 10.0
34 spasticity 10.0
35 tremor 10.0
36 spastic paraplegia 73, autosomal dominant 10.0 ATP13A2 FA2H
37 spastic paraplegia 76, autosomal recessive 10.0 ATP13A2 FA2H
38 early-onset parkinson's disease 10.0 ATP13A2 SNCA
39 leukodystrophy, hypomyelinating, 2 10.0 FA2H PANK2 VPS13A
40 movement disease 9.9 FTL PANK2 SNCA SNCG
41 3-methylglutaconic aciduria, type iii 9.9 C19orf12 FA2H PANK2 PLA2G6 SNCA
42 parkinson disease 15, autosomal recessive early-onset 9.9 ATP13A2 C19orf12 PANK2 PLA2G6 SNCA
43 dementia, lewy body 9.8 SNCA SNCB SNCG
44 spastic paraparesis 9.8 DDHD1 FA2H
45 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 9.7 DDHD1 FA2H
46 synucleinopathy 9.7 ATP13A2 SNCA SNCB SNCG
47 parkinson disease, late-onset 9.7 ATP13A2 SNCA SNCB SNCG
48 hereditary spastic paraplegia 9.6 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 spasticity 32 frequent (33%) HP:0001257
2 dysarthria 32 frequent (33%) HP:0001260
3 chorea 32 frequent (33%) HP:0002072
4 optic atrophy 32 frequent (33%) HP:0000648
5 retinopathy 32 frequent (33%) HP:0000488
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 cerebellar atrophy 32 frequent (33%) HP:0001272
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
Iron Approved Phase 3,Phase 2 7439-89-6 23925
2
Deferiprone Approved Phase 3,Phase 2 30652-11-0 2972
3 Iron Chelating Agents Phase 3,Phase 2
4 Pharmaceutical Solutions Phase 3,Phase 2
5 Chelating Agents 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 Active, not 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, Subthalamic Nucleus

Publications for Neurodegeneration with Brain Iron Accumulation

Articles related to Neurodegeneration with Brain Iron Accumulation:

(show top 50) (show all 126)
# 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
Visual and ocular motor function in the atypical form of neurodegeneration with brain iron accumulation type I. ( 28487376 )
2018
6
Neurodegeneration With Brain Iron Accumulation: A Novel Mutation in the Ceruloplasmin Gene. ( 30383083 )
2018
7
Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing. ( 30392167 )
2018
8
Classification and molecular pathogenesis of NBIA syndromes. ( 29409688 )
2018
9
Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient. ( 29681108 )
2018
10
A new NBIA patient from Turkey with homozygous C19ORF12 mutation. ( 30298423 )
2018
11
On the complexity of clinical and molecular bases of neurodegeneration with brain iron accumulation. ( 28542792 )
2017
12
A homozygous splice variant in AP4S1 mimicking neurodegeneration with brain iron accumulation. ( 28150420 )
2017
13
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
14
Neurodegeneration with brain iron accumulation. ( 28987166 )
2017
15
Extending the aceruloplasminemia phenotype: NBIA on imaging and acanthocytosis, yet only minor neurological findings. ( 28431603 )
2017
16
Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation. ( 28818478 )
2017
17
Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories. ( 25870938 )
2016
18
Neurodegeneration with brain iron accumulation (NBIA) formerly Hallervorden- Spatz disease. ( 27728536 )
2016
19
Mitochondrial dysfunction and defects in lipid homeostasis as therapeutic targets in neurodegeneration with brain iron accumulation. ( 27141409 )
2016
20
Neurodegeneration with brain iron accumulation. ( 27487369 )
2016
21
Neurodegeneration with Brain Iron Accumulation. ( 26739693 )
2016
22
Severe early basal ganglia hypometabolism in neurodegeneration with brain iron accumulation. ( 26993314 )
2016
23
Neurodegeneration with brain iron accumulation presenting motor trick and impaired motor cortical plasticity. ( 26773698 )
2016
24
Neurodegeneration with brain iron accumulation: A case report. ( 29213449 )
2016
25
A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging. ( 27487380 )
2016
26
Down-regulation of coasy, the gene associated with NBIA-VI, reduces Bmp signaling, perturbs dorso-ventral patterning and alters neuronal development in zebrafish. ( 27892483 )
2016
27
SCP2 mutations and neurodegeneration with brain iron accumulation. ( 26497993 )
2015
28
Aceruloplasminemia: neurodegeneration with brain iron accumulation (NBIA) associated with parkinsonism. ( 25413956 )
2015
29
Mitochondria: A crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases. ( 25668476 )
2015
30
Self-Mutilation in Neurodegeneration with Brain Iron Accumulation. ( 26120159 )
2015
31
Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation. ( 25592411 )
2015
32
Role of A^a8,F-FDG PET imaging in paediatric primary dystonia and dystonia arising from neurodegeneration with brain iron accumulation. ( 25646707 )
2015
33
Neurodegeneration with brain iron accumulation: diagnosis and management. ( 25614780 )
2015
34
C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation. ( 25962551 )
2015
35
Neurodegeneration with Brain Iron Accumulation: Genetic Diversity and Pathophysiological Mechanisms. ( 25973518 )
2015
36
Defective lipid metabolism in neurodegeneration with brain iron accumulation (NBIA) syndromes: not only a matter of iron. ( 25300979 )
2015
37
Neurodegeneration with Brain Iron Accumulation: Clinicoradiological Approach to Diagnosis. ( 25545045 )
2015
38
Ophthalmic features of PLA2G6-related paediatric neurodegeneration with brain iron accumulation. ( 24522175 )
2014
39
Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. ( 24360804 )
2014
40
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
41
Proceedings of the third joint symposium on neuroacanthocytosis and neurodegeneration with brain iron accumulation: from benchside to bedside. ( 25621189 )
2014
42
Neurodegeneration with brain iron accumulation: an overview. ( 25657764 )
2014
43
Neurodegeneration with brain iron accumulation in an eleven-year-old jamaican male. ( 24600523 )
2014
44
Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms. ( 24847269 )
2014
45
Adult-onset case of undiagnosed neurodegeneration with brain iron accumulation with psychotic symptoms. ( 24963432 )
2014
46
Update on neurodegeneration with brain iron accumulation. ( 24981186 )
2014
47
Alteration of the coenzyme A biosynthetic pathway in neurodegeneration with brain iron accumulation syndromes. ( 25110004 )
2014
48
Neurodegeneration with brain iron accumulation disorder mimics autism. ( 25456304 )
2014
49
Clinical features of neurodegeneration with brain iron accumulation due to a C19orf12 gene mutation. ( 23494994 )
2013
50
Psychotic Disorder in Neurodegeneration with Brain Iron Accumulation. ( 24047758 )
2013

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
3 CRAT NM_000755.4(CRAT): c.962G> A (p.Arg321His) single nucleotide variant Pathogenic rs138665095 GRCh38 Chromosome 9, 129100533: 129100533
4 CRAT NM_000755.4(CRAT): c.962G> A (p.Arg321His) single nucleotide variant Pathogenic rs138665095 GRCh37 Chromosome 9, 131862812: 131862812
5 REPS1 NM_001286611.1(REPS1): c.338C> A (p.Ala113Glu) single nucleotide variant Pathogenic rs201191394 GRCh37 Chromosome 6, 139266774: 139266774
6 REPS1 NM_001286611.1(REPS1): c.338C> A (p.Ala113Glu) single nucleotide variant Pathogenic rs201191394 GRCh38 Chromosome 6, 138945637: 138945637

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

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

# Super pathways Score Top Affiliating Genes
1 10.56 FTL SLC39A14
2 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 CRAT PANK2 PLA2G6 SNCA
2 cytosol GO:0005829 9.4 C19orf12 COASY CRAT DDHD1 FTL PANK2
3 inclusion body GO:0016234 8.96 SNCA SNCB

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.81 CRAT DDHD1 FA2H PLA2G6
2 autophagy GO:0006914 9.61 C19orf12 VPS13A WDR45
3 fatty acid metabolic process GO:0006631 9.58 CRAT FA2H SNCA
4 synaptic vesicle endocytosis GO:0048488 9.49 SNCA SNCB
5 regulation of dopamine secretion GO:0014059 9.48 SNCA SNCG
6 cellular zinc ion homeostasis GO:0006882 9.46 ATP13A2 SLC39A14
7 regulation of neurotransmitter secretion GO:0046928 9.37 SNCA SNCG
8 iron ion transport GO:0006826 9.32 FTL SLC39A14
9 dopamine metabolic process GO:0042417 9.26 SNCA SNCB
10 coenzyme A biosynthetic process GO:0015937 9.16 COASY PANK2
11 coenzyme biosynthetic process GO:0009108 8.96 COASY PANK2
12 synapse organization GO:0050808 8.8 SNCA SNCB SNCG

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 9.16 ATP13A2 WDR45
2 ferrous iron binding GO:0008198 8.96 FTL SNCA
3 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
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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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