NBIA1
MCID: NRD017
MIFTS: 61

Neurodegeneration with Brain Iron Accumulation 1 (NBIA1)

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

Aliases & Classifications for Neurodegeneration with Brain Iron Accumulation 1

MalaCards integrated aliases for Neurodegeneration with Brain Iron Accumulation 1:

Name: Neurodegeneration with Brain Iron Accumulation 1 56 12 73 29 13
Pantothenate Kinase-Associated Neurodegeneration 56 12 74 24 52 25 53 58 73 36 43 15
Hallervorden-Spatz Disease 56 12 52 53 54 32
Pkan 56 24 52 25 58 73
Nbia1 56 12 25 58 73
Hallervorden-Spatz Syndrome 12 58 73 71
Pigmentary Pallidal Degeneration 12 29 6
Neurodegeneration with Brain Iron Accumulation Type 1 25 58
Neurodegeneration with Brain Iron Accumulation Type 1, Atypical Form 58
Neurodegeneration with Brain Iron Accumulation Type 1, Classic Form 58
Atypical Pantothenate Kinase-Associated Neurodegeneration 58
Classic Pantothenate Kinase-Associated Neurodegeneration 58
Neurodegeneration, with Brain Iron Accumulation, Type 1 39
Pantothenate Kinase-Associated Neurodegeneration; Pkan 56
Neurodegeneration with Brain Iron Accumulation 52
Pkan Neuroaxonal Dystrophy, Juvenile-Onset 56
Pkan Neuroaxonal Dystrophy Juvenile-Onset 73
Brain Iron Accumulation Type I Syndrome 12
Neuroaxonal Dystrophy, Late Infantile 52
Nbia1, Atypical Form 58
Nbia1, Classic Form 58
Pkan, Atypical Form 58
Pkan, Classic Form 58
Nbia 52
Hss 73

Characteristics:

Orphanet epidemiological data:

58
pantothenate kinase-associated neurodegeneration
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: All ages; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
clinically classified into classic, atypical, and intermediate phenotypes
classic: onset in first decade, rapid progression, loss of independent ambulation within 15 years
atypical: onset in second decade, slow progression, maintenance of independent ambulation up to 40 years later
intermediate: onset in first decade with slow progression or onset in second decade with rapid progression
allelic to the less severe harp syndrome , which is distinguished by the presence of hypobetalipoproteinemia and acanthocytosis
similar to infantile neuroaxonal dystrophy (inad, )


HPO:

31
neurodegeneration with brain iron accumulation 1:
Inheritance autosomal recessive inheritance
Onset and clinical course rapidly progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Neurodegeneration with Brain Iron Accumulation 1

Genetics Home Reference : 25 Pantothenate kinase-associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) is a disorder of the nervous system. This condition is characterized by progressive difficulty with movement, typically beginning in childhood. Movement abnormalities include involuntary muscle spasms, rigidity, and trouble with walking that worsens over time. Many people with this condition also develop problems with speech (dysarthria), and some develop vision loss. Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression. Pantothenate kinase-associated neurodegeneration is characterized by an abnormal buildup of iron in certain areas of the brain. A particular change called the eye-of-the-tiger sign, which indicates an accumulation of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder. Researchers have described classic and atypical forms of pantothenate kinase-associated neurodegeneration. The classic form usually appears in early childhood, causing severe problems with movement that worsen rapidly. Features of the atypical form appear later in childhood or adolescence and progress more slowly. Signs and symptoms vary, but the atypical form is more likely than the classic form to involve speech defects and psychiatric problems. A condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration), which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration. Although HARP is much rarer than classic pantothenate kinase-associated neurodegeneration, both conditions involve problems with movement, dementia, and vision abnormalities.

MalaCards based summary : Neurodegeneration with Brain Iron Accumulation 1, also known as pantothenate kinase-associated neurodegeneration, is related to oromandibular dystonia and mcleod syndrome, and has symptoms including ataxia, tremor and involuntary movements. An important gene associated with Neurodegeneration with Brain Iron Accumulation 1 is PANK2 (Pantothenate Kinase 2), and among its related pathways/superpathways are Pantothenate and CoA biosynthesis and Metabolism of water-soluble vitamins and cofactors. The drugs Deferiprone and Folic acid have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and skin, and related phenotypes are gait disturbance and iris hypopigmentation

Disease Ontology : 12 A neurodegeneration with brain iron accumulation that has material basis in autosomal recessive inheritance of mutation in the PANK2 gene on chromosome 20p13.

NIH Rare Diseases : 52 Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease characterized by a progressive degeneration of the nervous system (neurodegenerative disorder) and buildup of iron in the brain. PKAN is usually classified into two forms: classic and atypical. Classic PKAN causes symptoms in the first ten years of life. The atypical form of PKAN usually occurs after the age of ten and progresses more slowly. All individuals with PKAN have an abnormal buildup of iron in certain areas of the brain. A particular change, called the eye-of-the-tiger sign , which indicates a buildup of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder. PKAN is inherited in an autosomal recessive manner and is caused by mutations in the PANK2 gene . Treatment depends on the symptoms, and may include medication (such as botulinum toxin ), surgery, deep brain stimulation and physical therapy . Research for a more effective treatment is ongoing.

OMIM : 56 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, severity, and cognitive involvement are variable (review by Gregory et al., 2009). Panthothenate kinase-associated neurodegeneration has been classified clinically as 'classic,' 'atypical,' or 'intermediate.' In the classic form, patients present within the first decade of life with rapidly progressing disease and loss of ambulation approximately 15 years later. In the atypical form, patients have onset in the second decade with slow progression and maintain independent ambulation after 15 years. In the intermediate form, patients have early onset and slow progression or later onset and rapid progression. Patients with early onset tend to develop pigmentary retinopathy, whereas those with later onset tend to have speech disorders and psychiatric features. All patients have the 'eye of the tiger' sign on brain MRI (Hayflick et al., 2003; Pellecchia et al., 2005). Kumar et al. (2006) noted that the 'eye of the tiger' sign is not pathognomonic for PANK2 mutations. They reported 2 unrelated adult patients with cognitive dysfunction who had the characteristic sign on MRI but did not have mutations in the PANK2 gene. Gregory et al. (2009) provided a detailed review of the different forms of neurodegeneration with brain iron accumulation. In addition, some patients with Kufor-Rakeb syndrome (606693), also known as Parkinson disease-9 (PARK9), have iron deposition in the basal ganglia. (234200)

NINDS : 53 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.

KEGG : 36 Pantothenate kinase associated neurodegeneration (PKAN), also known as Hallervorden-Spatz disease, is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Mutations in PANK2 gene encoding the mitochondrial pantothenate kinase have been found in patients.

UniProtKB/Swiss-Prot : 73 Neurodegeneration with brain iron accumulation 1: Autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. Clinical manifestations include progressive muscle spasticity, hyperreflexia, muscle rigidity, dystonia, dysarthria, and intellectual deterioration which progresses to severe dementia over several years. It is clinically classified into classic, atypical, and intermediate phenotypes. Classic forms present with onset in first decade, rapid progression, loss of independent ambulation within 15 years. Atypical forms have onset in second decade, slow progression, maintenance of independent ambulation up to 40 years later. Intermediate forms manifest onset in first decade with slow progression or onset in second decade with rapid progression. Patients with early onset tend to also develop pigmentary retinopathy, whereas those with later onset tend to also have speech disorders and psychiatric features. All patients have the 'eye of the tiger' sign on brain MRI.

Wikipedia : 74 Pantothenate kinase-associated neurodegeneration (PKAN), formerly called Hallervorden-Spatz syndrome, is... more...

GeneReviews: NBK1490

Related Diseases for Neurodegeneration with Brain Iron Accumulation 1

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 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 211)
# Related Disease Score Top Affiliating Genes
1 oromandibular dystonia 30.9 PLA2G6 PANK2 C19orf12
2 mcleod syndrome 30.4 XK VPS13A
3 alcohol-related neurodevelopmental disorder 30.3 WDR45 C19orf12
4 lingual-facial-buccal dyskinesia 30.3 XK VPS13A
5 spastic paraplegia 35, autosomal recessive 30.2 WDR45 PLA2G6 PANK2 FA2H DCAF17 COASY
6 neurodegeneration with brain iron accumulation 6 30.0 WDR45 PLA2G6 PANK2 PANK1 FA2H DCAF17
7 iron metabolism disease 29.7 PANK2 FTL CP
8 hereditary spastic paraplegia 29.7 PLA2G6 FA2H C19orf12 ATP13A2
9 neurodegeneration with brain iron accumulation 5 29.3 WDR45 PLA2G6 PANK2 PANK1 FA2H DCAF17
10 choreatic disease 29.3 XK VPS13A PANK2 JPH3 FTL
11 neurodegeneration with brain iron accumulation 4 28.9 WDR45 PLA2G6 PANK2 PANK1 FTL FA2H
12 movement disease 28.9 VPS13A SNCA PLA2G6 PANK2 FTL CP
13 dementia 28.8 SNCA JPH3 CP ATP13A2
14 choreoacanthocytosis 28.6 XK VPS13A PANK2 PANK1 JPH3 FTL
15 neurodegeneration with brain iron accumulation 2b 28.5 PLA2G6 PANK4 PANK2 PANK1 FTL FA2H
16 neuroaxonal dystrophy 28.0 WDR45 SNCA PLA2G6 PANK2 PANK1 FTL
17 kufor-rakeb syndrome 27.6 WDR45 SNCA PLA2G6 PANK2 PANK1 FTL
18 neurodegeneration with brain iron accumulation 2a 27.4 WDR45 SNCA PLA2G6 PANK2 PANK1 FTL
19 dystonia 26.3 XK WDR45 VPS13A PLA2G6 PANK2 JPH3
20 neurodegeneration with brain iron accumulation 3 26.3 WDR45 PLA2G6 PANK2 PANK1 JPH3 FTL
21 aceruloplasminemia 24.4 WDR45 VPS13A SNCA PLA2G6 PANK4 PANK3
22 neurodegeneration with brain iron accumulation 23.8 XK WDR45 VPS13A SNCA PLA2G6 PANK4
23 neurodegeneration with brain iron accumulation 7 13.1
24 neurodegeneration with brain iron accumulation 8 13.1
25 woodhouse-sakati syndrome 11.8
26 hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration 11.7
27 karak syndrome 11.7
28 hallermann-streiff syndrome 11.6
29 striatonigral degeneration, infantile 11.4
30 hoyeraal hreidarsson syndrome 11.3
31 hypotrichosis simplex 11.3
32 retinal degeneration 10.6
33 spasticity 10.6
34 autosomal recessive disease 10.5
35 3-methylglutaconic aciduria, type iii 10.5
36 tremor 10.5
37 ferro-cerebro-cutaneous syndrome 10.5
38 amyotrophic lateral sclerosis 1 10.5
39 huntington disease 10.5
40 lateral sclerosis 10.5
41 retinitis pigmentosa 10.5
42 neuroretinitis 10.4
43 retinitis 10.4
44 leukodystrophy 10.4
45 spastic diplegia 10.4
46 psychotic disorder 10.4
47 encephalitis 10.4
48 cerebral atrophy 10.4
49 down syndrome 10.4
50 ataxia and polyneuropathy, adult-onset 10.4

Graphical network of the top 20 diseases related to Neurodegeneration with Brain Iron Accumulation 1:



Diseases related to Neurodegeneration with Brain Iron Accumulation 1

Symptoms & Phenotypes for Neurodegeneration with Brain Iron Accumulation 1

Human phenotypes related to Neurodegeneration with Brain Iron Accumulation 1:

58 31 (show top 50) (show all 89)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Occasional (29-5%) HP:0001288
2 iris hypopigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007730
3 spasticity 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%),Frequent (79-30%) HP:0001257
4 hyperreflexia 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%),Frequent (79-30%) HP:0001347
5 emotional lability 58 31 frequent (33%) Frequent (79-30%) HP:0000712
6 depressivity 58 31 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0000716
7 dysarthria 58 31 occasional (7.5%) Occasional (29-5%),Frequent (79-30%),Frequent (79-30%) HP:0001260
8 tremor 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0001337
9 dysphagia 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%),Occasional (29-5%) HP:0002015
10 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
11 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
12 rod-cone dystrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000510
13 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
14 cognitive impairment 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0100543
15 irritability 58 31 frequent (33%) Frequent (79-30%) HP:0000737
16 attention deficit hyperactivity disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007018
17 abnormality of the foot 58 31 frequent (33%) Frequent (79-30%) HP:0001760
18 inability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0002540
19 toe walking 58 31 frequent (33%) Frequent (79-30%) HP:0040083
20 muscle stiffness 58 31 frequent (33%) Frequent (79-30%) HP:0003552
21 rigidity 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002063
22 abnormal cranial nerve morphology 58 31 frequent (33%) Frequent (79-30%) HP:0001291
23 increased susceptibility to fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002659
24 impulsivity 58 31 frequent (33%) Frequent (79-30%) HP:0100710
25 choreoathetosis 58 31 frequent (33%) Frequent (79-30%) HP:0001266
26 optic disc pallor 58 31 frequent (33%) Frequent (79-30%) HP:0000543
27 abnormality of the tongue 58 31 frequent (33%) Frequent (79-30%) HP:0000157
28 frequent falls 58 31 frequent (33%) Frequent (79-30%),Very rare (<4-1%) HP:0002359
29 generalized dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0007325
30 iron accumulation in brain 58 31 frequent (33%) Frequent (79-30%) HP:0012675
31 parkinsonism 58 31 frequent (33%) Frequent (79-30%) HP:0001300
32 abnormal posturing 58 31 frequent (33%) Frequent (79-30%) HP:0002533
33 limb dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0002451
34 eye of the tiger anomaly of globus pallidus 58 31 frequent (33%) Frequent (79-30%) HP:0002454
35 violent behavior 58 31 frequent (33%) Frequent (79-30%) HP:0008760
36 pigmentary retinopathy 31 frequent (33%) HP:0000580
37 joint dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001373
38 seizures 58 31 occasional (7.5%) Occasional (29-5%),Very rare (<4-1%) HP:0001250
39 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
40 abnormal pyramidal sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0007256
41 dysphonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001618
42 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
43 developmental regression 58 31 occasional (7.5%) Occasional (29-5%) HP:0002376
44 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
45 visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000505
46 weight loss 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0001824
47 abnormality of skin pigmentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001000
48 cachexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0004326
49 cough 58 31 occasional (7.5%) Occasional (29-5%) HP:0012735
50 mask-like facies 58 31 occasional (7.5%) Occasional (29-5%) HP:0000298

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
ataxia
dysarthria
tremor
dystonia
more
Abdomen Gastrointestinal:
dysphagia
feeding difficulties

Muscle Soft Tissue:
decreased muscle mass
myopathic changes seen on muscle biopsy

Genitourinary Bladder:
urinary incontinence

Skeletal Feet:
foot deformity

Voice:
dysphonia

Head And Neck Eyes:
retinal degeneration
optic atrophy
blepharospasm
pigmentary retinopathy (more common in classic disease)
apraxia of eyelid opening

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity
obsessive-compulsive trait
depression
behavioral problems
psychiatric abnormalities (more common in patients with atypical disease and slow progression)

Head And Neck Face:
facial grimacing

Skin Nails Hair Skin:
skin pigmentation

Clinical features from OMIM:

234200

UMLS symptoms related to Neurodegeneration with Brain Iron Accumulation 1:


ataxia, tremor, involuntary movements, muscle rigidity, muscle spasticity, stiffness, tic, motor

GenomeRNAi Phenotypes related to Neurodegeneration with Brain Iron Accumulation 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance GR00297-A 8.92 PANK1 PANK2 PANK4 PLA2G6

MGI Mouse Phenotypes related to Neurodegeneration with Brain Iron Accumulation 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.32 ATP13A2 CP FA2H JPH3 PANK1 PANK2

Drugs & Therapeutics for Neurodegeneration with Brain Iron Accumulation 1

Drugs for Neurodegeneration with Brain Iron Accumulation 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Deferiprone Approved Phase 3 30652-11-0 2972
2
Folic acid Approved, Nutraceutical, Vet_approved Phase 3 59-30-3 6037
3
Pantothenic acid Approved, Nutraceutical, Vet_approved Phase 3 79-83-4 6613
4 Chelating Agents Phase 3
5 Iron Chelating Agents Phase 3
6 Pharmaceutical Solutions Phase 3
7 Vitamins Phase 3
8 Vitamin B Complex Phase 3
9 Vitamin B9 Phase 3
10 Folate Phase 3
11
Iron Approved, Experimental 7439-89-6, 15438-31-0 23925 27284
12 Strawberry Approved
13
Vitamin A Approved, Nutraceutical, Vet_approved 68-26-8, 11103-57-4, 22737-96-8 445354 9904001
14 retinol
15 Retinol palmitate
16 Micronutrients
17 Trace Elements
18 Nutrients

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Long-term Safety and Efficacy Study of Deferiprone in Patients With Pantothenate Kinase-Associated Neurodegeneration (PKAN) Completed NCT02174848 Phase 3 Deferiprone oral solution
2 A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN) Completed NCT01741532 Phase 3 Deferiprone oral solution;Placebo
3 Efficacy and Safety of the Iron Chelator Deferiprone on Iron Overload in the Brain in Parkinson's Disease Completed NCT00943748 Phase 2, Phase 3 deferiprone;placebo
4 Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), A Phosphopantothenate Replacement Therapy, in Pantothenate Kinase-Associated Neurodegeneration (PKAN) Patients: A Randomized, Double Blind, Placebo Controlled Study With an Open Label Extension 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 Protocol RT001-009: A Natural History Study of Infantile Neuroaxonal Dystrophy Recruiting NCT04027816
9 The Compassionate Use of Deferiprone in Patients With Pantothenate Kinase-Associated Neurodegeneration Available NCT02635841 Deferiprone
10 A Phase 2 Study of a Vitamin Metabolite for PKAN Not yet recruiting NCT04182763
11 Imaging Neuromelanin and Iron in Dystonia/Parkinsonism Not yet recruiting NCT03572114

Search NIH Clinical Center for Neurodegeneration with Brain Iron Accumulation 1

Cochrane evidence based reviews: pantothenate kinase-associated neurodegeneration

Genetic Tests for Neurodegeneration with Brain Iron Accumulation 1

Genetic tests related to Neurodegeneration with Brain Iron Accumulation 1:

# Genetic test Affiliating Genes
1 Pigmentary Pallidal Degeneration 29 PANK2
2 Neurodegeneration with Brain Iron Accumulation 1 29

Anatomical Context for Neurodegeneration with Brain Iron Accumulation 1

MalaCards organs/tissues related to Neurodegeneration with Brain Iron Accumulation 1:

40
Brain, Eye, Skin, Globus Pallidus, Tongue, Liver, Testes

Publications for Neurodegeneration with Brain Iron Accumulation 1

Articles related to Neurodegeneration with Brain Iron Accumulation 1:

(show top 50) (show all 329)
# Title Authors PMID Year
1
A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect. 54 61 24 56 6
16240131 2005
2
A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. 54 24 56 6
11479594 2001
3
Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. 54 61 56 6
12510040 2003
4
Syndromes of neurodegeneration with brain iron accumulation. 61 56 6
22704258 2012
5
The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration. 54 61 56
15911822 2005
6
Hallervorden and history. 24 56
12510036 2003
7
Clinical and genetic delineation of neurodegeneration with brain iron accumulation. 61 56
18981035 2009
8
Biochemical properties of human pantothenate kinase 2 isoforms and mutations linked to pantothenate kinase-associated neurodegeneration. 54 61 24
16272150 2006
9
[123I]FP-CIT SPECT findings in two patients with Hallervorden-Spatz disease with homozygous mutation in PANK2 gene. 54 56
15642932 2005
10
Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. 61 56
15525657 2005
11
Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic. 54 6
14638969 2003
12
Pantothenate Kinase-Associated Neurodegeneration 61 6
20301663 2002
13
Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. 56
29395073 2018
14
Consensus clinical management guideline for pantothenate kinase-associated neurodegeneration (PKAN). 61 24
28034613 2017
15
Pallidal neuronal apolipoprotein E in pantothenate kinase-associated neurodegeneration recapitulates ischemic injury to the globus pallidus. 61 24
26547561 2015
16
Deep brain stimulation for pantothenate kinase-associated neurodegeneration. 61 24
25802776 2015
17
Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic. 61 24
25915509 2015
18
Does lesioning surgery have a role in the management of multietiological tremor in the era of Deep Brain Stimulation? 61 24
25128653 2014
19
Idiopathic basal ganglia calcifications: an atypical presentation of PKAN. 61 24
23968566 2013
20
Neurodegeneration with Brain Iron Accumulation Disorders Overview 6
23447832 2013
21
New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. 61 24
23269600 2013
22
Missense PANK2 mutation without "eye of the tiger" sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN). 61 24
22127788 2012
23
Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation. 61 24
22103354 2012
24
Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: results of a phase II pilot trial. 61 24
21557313 2011
25
The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration. 61 24
21877312 2011
26
Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration. 61 24
21459825 2011
27
Intellectual and adaptive behaviour functioning in pantothenate kinase-associated neurodegeneration. 61 24
17493025 2007
28
Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. 56
16437574 2006
29
The "eye-of-the-tiger" sign is not pathognomonic of the PANK2 mutation. 56
16476823 2006
30
Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). 61 24
16023068 2005
31
Pantothenate kinase-associated neurodegeneration initially presenting as postural tremor alone in a Japanese family with homozygous N245S substitutions in the pantothenate kinase gene. 61 24
15465096 2004
32
HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. 61 24
12058097 2002
33
Hallervorden-Spatz syndrome. 54 24
11551740 2001
34
Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. 56
8944032 1996
35
Myopathic involvement in two cases of Hallervorden-Spatz disease. 56
7503394 1995
36
Acanthocytosis, retinitis pigmentosa, and pallidal degeneration: a report of three patients, including the second reported case with hypoprebetalipoproteinemia (HARP syndrome). 6
7898702 1995
37
Optic atrophy as the presenting sign in Hallervorden-Spatz syndrome. 56
7885538 1994
38
Julius Hallervorden. 56
8327163 1993
39
Racial hygiene, active euthanasia, and Julius Hallervorden. 56
1436542 1992
40
Hallervorden-Spatz disease: clinical and MRI study of 11 cases diagnosed in life. 56
1447570 1992
41
Hallervorden-Spatz syndrome: clinical and magnetic resonance imaging correlations. 56
3202617 1988
42
MR imaging in a case of Hallervorden-Spatz disease. 56
3680689 1987
43
MR imaging of Hallervorden-Spatz disease. 56
3989044 1985
44
Late-onset Hallervorden-Spatz disease presenting as familial parkinsonism. 56
3969211 1985
45
Neuroaxonal dystrophy in childhood. Report of two second cousins with Hallerworden-Spatz disease, and a case of Seitelberger's disease. 56
7158329 1982
46
Hallervorden-Spatz disease. 56
477009 1979
47
Basal ganglia calcification in a case of PKAN. 24
28024710 2017
48
Adult onset Hallervorden-Spatz disease with psychotic symptoms. 24
21769749 2011
49
ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. 24
20310007 2010
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Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: clinical features and (99m)Tc-ECD brain perfusion SPECT findings. 54 61
20006850 2010

Variations for Neurodegeneration with Brain Iron Accumulation 1

ClinVar genetic disease variations for Neurodegeneration with Brain Iron Accumulation 1:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PANK2 NM_153638.3(PANK2):c.930_936del (p.Phe311fs)deletion Pathogenic 4547 rs879253712 20:3888871-3888877 20:3908224-3908230
2 PANK2 NM_153638.3(PANK2):c.1561G>A (p.Gly521Arg)SNV Pathogenic 4548 rs137852959 20:3899342-3899342 20:3918695-3918695
3 PANK2 NM_153638.3(PANK2):c.570C>G (p.Tyr190Ter)SNV Pathogenic 4549 rs137852960 20:3870317-3870317 20:3889670-3889670
4 PANK2 NM_153638.3(PANK2):c.790C>T (p.Arg264Trp)SNV Pathogenic 4550 rs137852961 20:3888734-3888734 20:3908087-3908087
5 PANK2 NM_153638.3(PANK2):c.856C>T (p.Arg286Cys)SNV Pathogenic 4551 rs137852962 20:3888800-3888800 20:3908153-3908153
6 PANK2 NM_153638.3(PANK2):c.1412G>A (p.Ser471Asn)SNV Pathogenic 4552 rs137852963 20:3893281-3893281 20:3912634-3912634
7 PANK2 NM_153638.3(PANK2):c.1583C>T (p.Thr528Met)SNV Pathogenic 4556 rs137852967 20:3899364-3899364 20:3918717-3918717
8 PANK2 NM_153638.3(PANK2):c.1441C>T (p.Arg481Ter)SNV Pathogenic 4557 rs137852968 20:3897602-3897602 20:3916955-3916955
9 PANK2 NM_153638.3(PANK2):c.1413-1G>TSNV Pathogenic 4559 rs148987163 20:3897573-3897573 20:3916926-3916926
10 PANK2 NM_153638.3(PANK2):c.1442_1444del (p.Arg481_Glu482delinsGln)deletion Pathogenic 4560 rs766251466 20:3897603-3897605 20:3916956-3916958
11 PANK2 NM_153638.3(PANK2):c.533C>A (p.Ser178Ter)SNV Pathogenic 4561 rs137852969 20:3870280-3870280 20:3889633-3889633
12 PANK2 NM_153638.3(PANK2):c.1426_1429del (p.Met476fs)deletion Pathogenic 417619 rs1555789557 20:3897587-3897590 20:3916940-3916943
13 PANK2 NM_153638.3(PANK2):c.1235+1G>TSNV Pathogenic 431115 rs1135401789 20:3891478-3891478 20:3910831-3910831
14 PANK2 NM_153638.3(PANK2):c.936T>A (p.Cys312Ter)SNV Pathogenic 437451 rs1555787799 20:3888880-3888880 20:3908233-3908233
15 PANK2 NM_153638.3(PANK2):c.1176_1177del (p.Gly393_Val394insTer)deletion Pathogenic 456524 rs778550409 20:3891418-3891419 20:3910771-3910772
16 PANK2 NM_153638.3(PANK2):c.680A>G (p.Tyr227Cys)SNV Pathogenic 456525 rs1555787646 20:3888624-3888624 20:3907977-3907977
17 PANK2 NM_153638.3(PANK2):c.1250_1251dup (p.Phe418fs)duplication Pathogenic 526628 rs1555788619 20:3893118-3893119 20:3912471-3912472
18 PANK2 NM_153638.3(PANK2):c.909del (p.Phe304fs)deletion Pathogenic 579971 rs1568569941 20:3888853-3888853 20:3908206-3908206
19 PANK2 NM_153638.3(PANK2):c.1257del (p.Phe419fs)deletion Pathogenic 573171 rs1568574931 20:3893120-3893120 20:3912473-3912473
20 PANK2 NM_153638.3(PANK2):c.1097del (p.Pro366fs)deletion Pathogenic 565372 rs753400880 20:3891337-3891337 20:3910690-3910690
21 PANK2 NM_153638.3(PANK2):c.126del (p.Arg44fs)deletion Pathogenic 642965 20:3869873-3869873 20:3889226-3889226
22 PANK2 NM_153638.3(PANK2):c.851_855dup (p.Arg286fs)duplication Pathogenic 664234 20:3888794-3888795 20:3908147-3908148
23 PANK2 NM_153638.3(PANK2):c.1211A>T (p.Asn404Ile)SNV Pathogenic 648367 20:3891453-3891453 20:3910806-3910806
24 PANK2 NC_000020.10:g.(?_3869728)_(3893301_?)deldeletion Pathogenic 526631 20:3869728-3893301 20:3889081-3912654
25 PANK2 NM_153638.3(PANK2):c.1236-2A>CSNV Pathogenic 526627 rs1261714833 20:3893103-3893103 20:3912456-3912456
26 PANK2 NM_153638.3(PANK2):c.1351C>T (p.Arg451Ter)SNV Pathogenic 667397 20:3893220-3893220 20:3912573-3912573
27 PANK2 NM_153638.3(PANK2):c.570_571del (p.Tyr190_Ser191delinsTer)deletion Pathogenic 803593 20:3870316-3870317 20:3889669-3889670
28 PANK2 NM_153638.3(PANK2):c.1085_1088del (p.Tyr362fs)deletion Pathogenic 807647 20:3891325-3891328 20:3910678-3910681
29 PANK2 NM_153638.3(PANK2):c.1086C>A (p.Tyr362Ter)SNV Pathogenic 807648 20:3891328-3891328 20:3910681-3910681
30 PANK2 NM_153638.3(PANK2):c.505_512del (p.Ser169fs)deletion Pathogenic/Likely pathogenic 504213 rs755653150 20:3870251-3870258 20:3889604-3889611
31 PANK2 NM_153638.3(PANK2):c.*40G>CSNV Likely pathogenic 430728 rs1131692166 20:3903981-3903981 20:3923334-3923334
32 PANK2 NM_153638.3(PANK2):c.1070G>C (p.Arg357Pro)SNV Likely pathogenic 803594 20:3891312-3891312 20:3910665-3910665
33 PANK2 NM_153638.3(PANK2):c.1481T>C (p.Leu494Ser)SNV Likely pathogenic 803595 20:3897642-3897642 20:3916995-3916995
34 PANK2 NM_153638.3(PANK2):c.1412+1G>CSNV Likely pathogenic 652533 20:3893282-3893282 20:3912635-3912635
35 PANK2 NM_153638.3(PANK2):c.1585A>G (p.Ile529Val)SNV Likely pathogenic 642654 20:3899366-3899366 20:3918719-3918719
36 PANK2 NM_153638.3(PANK2):c.644G>A (p.Gly215Glu)SNV Conflicting interpretations of pathogenicity 429264 rs762879569 20:3888588-3888588 20:3907941-3907941
37 PANK2 NM_153638.3(PANK2):c.1133A>G (p.Asp378Gly)SNV Conflicting interpretations of pathogenicity 225428 rs562740927 20:3891375-3891375 20:3910728-3910728
38 PANK2 NM_153638.3(PANK2):c.54A>G (p.Ser18=)SNV Uncertain significance 338357 rs886056650 20:3869801-3869801 20:3889154-3889154
39 PANK2 NM_153638.3(PANK2):c.954G>A (p.Ala318=)SNV Uncertain significance 338362 rs78631398 20:3888898-3888898 20:3908251-3908251
40 PANK2 NM_153638.3(PANK2):c.1684G>A (p.Ala562Thr)SNV Uncertain significance 338365 rs886056652 20:3903912-3903912 20:3923265-3923265
41 PANK2 NM_153638.3(PANK2):c.*541C>TSNV Uncertain significance 338371 rs886056655 20:3904482-3904482 20:3923835-3923835
42 PANK2 NM_153638.3(PANK2):c.*382C>TSNV Uncertain significance 338369 rs71647861 20:3904323-3904323 20:3923676-3923676
43 PANK2 NM_153638.3(PANK2):c.272C>T (p.Pro91Leu)SNV Uncertain significance 338358 rs757651957 20:3870019-3870019 20:3889372-3889372
44 PANK2 NM_153638.3(PANK2):c.*376A>GSNV Uncertain significance 338368 rs746515620 20:3904317-3904317 20:3923670-3923670
45 PANK2 NM_153638.3(PANK2):c.*407A>GSNV Uncertain significance 338370 rs886056654 20:3904348-3904348 20:3923701-3923701
46 PANK2 NM_153638.3(PANK2):c.628+15G>CSNV Uncertain significance 338361 rs566953264 20:3870390-3870390 20:3889743-3889743
47 PANK2 NM_153638.3(PANK2):c.1318C>T (p.Arg440Cys)SNV Uncertain significance 338363 rs201329683 20:3893187-3893187 20:3912540-3912540
48 PANK2 NM_153638.3(PANK2):c.1064A>G (p.Asn355Ser)SNV Uncertain significance 566107 rs746484727 20:3891306-3891306 20:3910659-3910659
49 PANK2 NM_153638.3(PANK2):c.1082A>G (p.Tyr361Cys)SNV Uncertain significance 575512 rs1568572918 20:3891324-3891324 20:3910677-3910677
50 PANK2 NM_153638.3(PANK2):c.1095C>G (p.Asn365Lys)SNV Uncertain significance 571421 rs1427550015 20:3891337-3891337 20:3910690-3910690

UniProtKB/Swiss-Prot genetic disease variations for Neurodegeneration with Brain Iron Accumulation 1:

73 (show all 30)
# Symbol AA change Variation ID SNP ID
1 PANK2 p.Gly219Val VAR_015154
2 PANK2 p.Thr234Ala VAR_015155 rs137852965
3 PANK2 p.Arg264Trp VAR_015156 rs137852961
4 PANK2 p.Arg278Cys VAR_015157 rs137852966
5 PANK2 p.Leu282Val VAR_015158
6 PANK2 p.Arg286Cys VAR_015159 rs137852962
7 PANK2 p.Thr327Ile VAR_015160
8 PANK2 p.Ser351Pro VAR_015161 rs137852964
9 PANK2 p.Asn355Ser VAR_015162 rs746484727
10 PANK2 p.Asn404Ile VAR_015163 rs752078407
11 PANK2 p.Leu413Pro VAR_015164 rs750176786
12 PANK2 p.Ser471Asn VAR_015165 rs137852963
13 PANK2 p.Ile497Thr VAR_015166
14 PANK2 p.Asn500Ile VAR_015167 rs759332123
15 PANK2 p.Gly521Arg VAR_015168 rs137852959
16 PANK2 p.Glu134Gly VAR_060934 rs765679726
17 PANK2 p.Arg249Pro VAR_060935
18 PANK2 p.Arg278Leu VAR_060936 rs134876220
19 PANK2 p.Glu322Asp VAR_060937 rs974575417
20 PANK2 p.Glu322Gly VAR_060938 rs768230831
21 PANK2 p.Arg357Gln VAR_060939 rs754521581
22 PANK2 p.Ala398Thr VAR_060940 rs759223327
23 PANK2 p.Cys428Tyr VAR_060942 rs101294710
24 PANK2 p.Asp447Asn VAR_060943
25 PANK2 p.Ile501Thr VAR_060944 rs775459398
26 PANK2 p.Ala509Val VAR_060945
27 PANK2 p.Asn511Asp VAR_060946 rs767653843
28 PANK2 p.Arg532Trp VAR_060947
29 PANK2 p.Leu563Pro VAR_060948 rs132407757
30 PANK2 p.Pro570Leu VAR_060949 rs41279408

Expression for Neurodegeneration with Brain Iron Accumulation 1

Search GEO for disease gene expression data for Neurodegeneration with Brain Iron Accumulation 1.

Pathways for Neurodegeneration with Brain Iron Accumulation 1

Pathways related to Neurodegeneration with Brain Iron Accumulation 1 according to KEGG:

36
# Name Kegg Source Accession
1 Pantothenate and CoA biosynthesis hsa00770

GO Terms for Neurodegeneration with Brain Iron Accumulation 1

Cellular components related to Neurodegeneration with Brain Iron Accumulation 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.73 WDR45 VPS13A SNCA PLA2G6 PANK4 PANK3
2 cell GO:0005623 9.28 XK VPS13A SNCA PLA2G6 MIR103A1 JPH3

Biological processes related to Neurodegeneration with Brain Iron Accumulation 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.8 PANK4 PANK3 PANK2 PANK1 COASY
2 autophagy GO:0006914 9.46 WDR45 VPS13A C19orf12 ATP13A2
3 positive regulation of exocytosis GO:0045921 9.43 SNCA PLA2G6
4 cellular iron ion homeostasis GO:0006879 9.43 FTL CP ATP13A2
5 regulation of neuronal synaptic plasticity GO:0048168 9.37 SNCA JPH3
6 iron ion transport GO:0006826 9.32 FTL CP
7 coenzyme biosynthetic process GO:0009108 9.13 PANK2 PANK1 COASY
8 coenzyme A biosynthetic process GO:0015937 9.02 PANK4 PANK3 PANK2 PANK1 COASY

Molecular functions related to Neurodegeneration with Brain Iron Accumulation 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 kinase activity GO:0016301 9.65 PANK4 PANK3 PANK2 PANK1 COASY
2 phosphatidylinositol-3,5-bisphosphate binding GO:0080025 9.37 WDR45 ATP13A2
3 ferrous iron binding GO:0008198 9.32 SNCA FTL
4 ferroxidase activity GO:0004322 9.16 FTL CP
5 acetyl-CoA binding GO:1905502 8.96 PANK3 PANK1
6 pantothenate kinase activity GO:0004594 8.92 PANK4 PANK3 PANK2 PANK1

Sources for Neurodegeneration with Brain Iron Accumulation 1

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