NBIA1
MCID: NRD017
MIFTS: 63

Neurodegeneration with Brain Iron Accumulation 1 (NBIA1)

Categories: Eye diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle 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 57 12 72 29 13
Pantothenate Kinase-Associated Neurodegeneration 57 12 73 25 20 43 53 58 72 36 44 15
Hallervorden-Spatz Disease 57 12 20 53 54 32
Pkan 57 25 20 43 58 72
Nbia1 57 12 43 58 72
Hallervorden-Spatz Syndrome 12 58 72 70
Pigmentary Pallidal Degeneration 12 29 6
Neurodegeneration with Brain Iron Accumulation Type 1 43 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 57
Neurodegeneration with Brain Iron Accumulation 20
Pkan Neuroaxonal Dystrophy, Juvenile-Onset 57
Pkan Neuroaxonal Dystrophy Juvenile-Onset 72
Brain Iron Accumulation Type I Syndrome 12
Neuroaxonal Dystrophy, Late Infantile 20
Nbia1, Atypical Form 58
Nbia1, Classic Form 58
Pkan, Atypical Form 58
Pkan, Classic Form 58
Nbia 20
Hss 72

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®:

57 (Updated 20-May-2021)
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

MedlinePlus Genetics : 43 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 spastic paraplegia 43, autosomal recessive and spastic paraplegia 35, autosomal recessive, 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 Strawberry 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 choreoathetosis

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.

GARD : 20 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® : 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, 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) (Updated 20-May-2021)

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.  Several genes have been found that cause NBIA.  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) ataxia (inability to coordinate movements) confusion seizures stupor dementia visual changes  Cognitive decline occurs in some forms of NBIA; the majority of individuals with NBIA do not have cognitive impairment.

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 : 72 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 : 73 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 225)
# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 43, autosomal recessive 31.0 PLA2G6 FA2H C19orf12
2 spastic paraplegia 35, autosomal recessive 30.6 WDR45 PLA2G6 PANK2 FA2H DCAF17 COASY
3 cerebral degeneration 30.6 SNCA PLA2G6 FA2H
4 blepharospasm 30.4 TOR1A PANK2
5 hereditary spastic paraplegia 30.4 PLA2G6 FA2H C19orf12 ATP13A2
6 alcohol-related neurodevelopmental disorder 30.4 WDR45 C19orf12
7 neurodegeneration with brain iron accumulation 4 30.3 WDR45 PLA2G6 PANK2 FTL FA2H DCAF17
8 iron metabolism disease 30.2 PANK2 FTL CP
9 lingual-facial-buccal dyskinesia 29.9 VPS13A PANK2 JPH3
10 neurodegeneration with brain iron accumulation 5 29.8 WDR45 PLA2G6 PANK2 PANK1 FA2H DCAF17
11 neurodegeneration with brain iron accumulation 6 29.6 WDR45 PLA2G6 PANK3 PANK2 PANK1 FA2H
12 neuroaxonal dystrophy 29.5 WDR45 SNCA PLA2G6 PANK2 PANK1 FTL
13 choreoacanthocytosis 29.3 VPS13A PANK2 PANK1 JPH3 FTL CP
14 parkinson disease, late-onset 29.1 TOR1A SNCA PLA2G6 CP ATP13A2
15 oromandibular dystonia 29.1 VPS13A TOR1A PLA2G6 PANK2 FA2H CP
16 neurodegeneration with brain iron accumulation 2b 28.7 PLA2G6 PANK3 PANK2 PANK1 FTL FA2H
17 kufor-rakeb syndrome 28.6 WDR45 SNCA PLA2G6 PANK2 PANK1 FA2H
18 movement disease 28.5 WDR45 VPS13A TOR1A SNCA PLA2G6 PANK2
19 acrocephalopolysyndactyly type iii 28.3 WDR45 PLA2G6 PANK2 PANK1 FTL FA2H
20 neurodegeneration with brain iron accumulation 2a 28.3 WDR45 PLA2G6 PANK2 PANK1 FTL FA2H
21 choreatic disease 28.1 VPS13A TOR1A SNCA PANK2 JPH3 FTL
22 dystonia 27.7 WDR45 VPS13A TOR1A PLA2G6 PANK2 JPH3
23 aceruloplasminemia 27.5 WDR45 VPS13A SNCA PLA2G6 PANK2 PANK1
24 neurodegeneration with brain iron accumulation 3 27.4 WDR45 PLA2G6 PANK2 PANK1 JPH3 FTL
25 neurodegeneration with brain iron accumulation 25.8 WDR45 VPS13A TOR1A SNCA PLA2G6 PANK4
26 neurodegeneration with brain iron accumulation 7 11.9
27 neurodegeneration with brain iron accumulation 8 11.9
28 hallermann-streiff syndrome 11.6
29 hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration 11.5
30 karak syndrome 11.5
31 woodhouse-sakati syndrome 11.3
32 striatonigral degeneration, infantile 11.3
33 hypotrichosis 11.1
34 hoyeraal hreidarsson syndrome 10.9
35 spasticity 10.6
36 retinal degeneration 10.5
37 tremor 10.5
38 3-methylglutaconic aciduria, type iii 10.5
39 leukodystrophy 10.5
40 retinitis pigmentosa 10.5
41 autosomal recessive disease 10.5
42 neuroretinitis 10.4
43 retinitis 10.4
44 paraplegia 10.4
45 abetalipoproteinemia 10.4
46 focal dystonia 10.4
47 azoospermia 10.4
48 amyotrophic lateral sclerosis 1 10.4
49 huntington disease 10.4
50 lateral sclerosis 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 112)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 spasticity 58 31 hallmark (90%) Frequent (79-30%),Frequent (79-30%),Very frequent (99-80%) HP:0001257
2 choreoathetosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001266
3 loss of ability to walk 58 31 hallmark (90%) Very frequent (99-80%) HP:0006957
4 retinal degeneration 58 31 hallmark (90%) Very frequent (99-80%) HP:0000546
5 eye of the tiger anomaly of globus pallidus 58 31 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0002454
6 hyperreflexia 58 31 occasional (7.5%) Frequent (79-30%),Frequent (79-30%),Occasional (29-5%) HP:0001347
7 emotional lability 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0000712
8 depressivity 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0000716
9 dysarthria 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%),Frequent (79-30%) HP:0001260
10 dysphagia 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0002015
11 osteopenia 58 31 frequent (33%) Frequent (79-30%) HP:0000938
12 cognitive impairment 58 31 frequent (33%) Frequent (79-30%),Occasional (29-5%) HP:0100543
13 attention deficit hyperactivity disorder 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0007018
14 irritability 58 31 frequent (33%) Frequent (79-30%) HP:0000737
15 toe walking 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0040083
16 muscle stiffness 58 31 frequent (33%) Frequent (79-30%) HP:0003552
17 bulbar signs 58 31 frequent (33%) Frequent (79-30%) HP:0002483
18 nyctalopia 58 31 frequent (33%) Frequent (79-30%) HP:0000662
19 abnormality of the tongue 58 31 frequent (33%) Frequent (79-30%) HP:0000157
20 acanthocytosis 58 31 frequent (33%) Frequent (79-30%) HP:0001927
21 rod-cone dystrophy 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000510
22 generalized dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0007325
23 optic disc pallor 58 31 frequent (33%) Frequent (79-30%) HP:0000543
24 rigidity 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002063
25 iron accumulation in brain 58 31 frequent (33%) Frequent (79-30%) HP:0012675
26 increased susceptibility to fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002659
27 pigmentary retinopathy 58 31 frequent (33%) Frequent (79-30%) HP:0000580
28 frequent falls 58 31 frequent (33%) Frequent (79-30%),Very rare (<4-1%) HP:0002359
29 limb dystonia 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002451
30 impulsivity 58 31 occasional (7.5%) Frequent (79-30%),Occasional (29-5%) HP:0100710
31 inability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0002540
32 peripheral visual field loss 58 31 frequent (33%) Frequent (79-30%) HP:0007994
33 parkinsonism 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001300
34 craniofacial dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0012179
35 limb pain 58 31 frequent (33%) Frequent (79-30%) HP:0009763
36 abetalipoproteinemia 58 31 frequent (33%) Frequent (79-30%) HP:0008181
37 retinal flecks 58 31 frequent (33%) Frequent (79-30%) HP:0012045
38 abnormal posturing 58 31 frequent (33%) Frequent (79-30%) HP:0002533
39 iron accumulation in substantia nigra 58 31 frequent (33%) Frequent (79-30%) HP:0012678
40 violent behavior 58 31 frequent (33%) Frequent (79-30%) HP:0008760
41 iron accumulation in globus pallidus 58 31 frequent (33%) Frequent (79-30%) HP:0012677
42 leg dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0031959
43 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
44 abnormal pyramidal sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0007256
45 gait disturbance 58 31 occasional (7.5%) Very frequent (99-80%),Occasional (29-5%),Very frequent (99-80%) HP:0001288
46 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
47 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
48 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001263
49 optic atrophy 58 31 occasional (7.5%) Very rare (<4-1%),Occasional (29-5%) HP:0000648
50 blindness 58 31 occasional (7.5%) Very rare (<4-1%),Very rare (<4-1%),Occasional (29-5%) HP:0000618

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
spasticity
ataxia
dysarthria
tremor
involuntary movements
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:
optic atrophy
blepharospasm
retinal degeneration
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 (Updated 20-May-2021)

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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.1 ATP13A2 COASY CP FA2H FTL JPH3
2 cellular MP:0005384 9.93 ATP13A2 COASY CP DCAF17 PANK1 PANK2
3 homeostasis/metabolism MP:0005376 9.77 ATP13A2 COASY CP FA2H FTL PANK1
4 nervous system MP:0003631 9.4 ATP13A2 COASY CP FA2H FTL JPH3

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 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Strawberry Approved
2
Deferiprone Approved 30652-11-0 2972
3
Iron Approved 7439-89-6 23925 29936
4
Vitamin A Approved, Nutraceutical, Vet_approved 68-26-8, 11103-57-4 445354
5 Retinol palmitate
6 retinol
7 Vitamins
8 Pharmaceutical Solutions
9 Chelating Agents
10 Iron Chelating Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 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
2 Long-term Safety and Efficacy Study of Deferiprone in Patients With Pantothenate Kinase-Associated Neurodegeneration (PKAN) Completed NCT02174848 Phase 3 Deferiprone oral solution
3 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 Terminated NCT03041116 Phase 3 Fosmetpantotenate;Placebo
4 Ferrochelating Treatment in Patients Affected by "Neurodegeneration With Brain Iron Accumulation" (NBIA) Active, not recruiting NCT00907283 Phase 2 Deferiprone
5 Brain Perfusion in Pantothenate Kinase-Associated Neurodegeneration (PKAN) Completed NCT01838018
6 NBIAready: Online Collection of Natural History Patient-reported Outcome Measures Recruiting NCT02587858
7 A Phase 2 Study of a Vitamin Metabolite for PKAN Recruiting NCT04182763
8 The Compassionate Use of Deferiprone in Patients With Pantothenate Kinase-Associated Neurodegeneration 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 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, Globus Pallidus, Tongue, Liver, Pancreas, Myeloid

Publications for Neurodegeneration with Brain Iron Accumulation 1

Articles related to Neurodegeneration with Brain Iron Accumulation 1:

(show top 50) (show all 350)
# 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. 61 54 25 57 6
16240131 2005
2
A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. 54 57 6 25
11479594 2001
3
The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration. 61 54 6 57
15911822 2005
4
Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. 54 57 6 61
12510040 2003
5
Biochemical properties of human pantothenate kinase 2 isoforms and mutations linked to pantothenate kinase-associated neurodegeneration. 25 54 6 61
16272150 2006
6
Deep brain stimulation for pantothenate kinase-associated neurodegeneration. 6 25 61
25802776 2015
7
Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic. 6 25 61
25915509 2015
8
Idiopathic basal ganglia calcifications: an atypical presentation of PKAN. 25 61 6
23968566 2013
9
Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation. 6 25 61
22103354 2012
10
Missense PANK2 mutation without "eye of the tiger" sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN). 6 61 25
22127788 2012
11
Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. 57 6
16437574 2006
12
Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). 61 6 25
16023068 2005
13
HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. 61 6 25
12058097 2002
14
Novel mutation in the PANK2 gene leads to pantothenate kinase-associated neurodegeneration in a Pakistani family. 54 6 61
17903678 2007
15
Hallervorden and history. 25 57
12510036 2003
16
Novel PANK2 mutation in a Chinese boy with PANK2-associated neurodegeneration: A case report and review of Chinese cases. 6 61
30681573 2019
17
[Phenotypic and genotypic features of twenty children with classic pantothenate kinase-associated neurodegeneration]. 61 6
28881514 2017
18
Novel PANK2 mutation in the first Greek compound heterozygote patient with pantothenate-kinase-associated neurodegeneration. 6 61
28781879 2017
19
A novel gene mutation in PANK2 in a patient with severe jaw-opening dystonia. 6 61
27185474 2016
20
Clinical Heterogeneity of Atypical Pantothenate Kinase-Associated Neurodegeneration in Koreans. 61 6
26828213 2016
21
A Novel Nonsense Mutation in PANK2 Gene in Two Patients with Pantothenate Kinase-Associated Neurodegeneration. 6 61
28357202 2016
22
Clinical, imaging, and molecular findings in a sample of Mexican families with pantothenate kinase-associated neurodegeneration. 6 61
24712887 2015
23
A novel gene mutation in PANK2 in a patient with an atypical form of pantothenate kinase-associated neurodegeneration. 61 6
24075960 2013
24
Late onset atypical pantothenate-kinase-associated neurodegeneration. 61 6
23634310 2013
25
Phenotypes and genotypes of patients with pantothenate kinase-associated neurodegeneration in Asian and Caucasian populations: 2 cases and literature review. 6 61
24348190 2013
26
Pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN): review of two major neurodegeneration with brain iron accumulation (NBIA) phenotypes. 61 6
24209433 2013
27
Motor activation in patients with Pantothenate-Kinase Associated Neurodegeneration: a functional magnetic resonance imaging study. 61 6
22682757 2012
28
Syndromes of neurodegeneration with brain iron accumulation. 61 57
22704258 2012
29
Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations. 6 61
22221393 2012
30
Childhood disorders of neurodegeneration with brain iron accumulation (NBIA). 6 61
21480873 2011
31
[Clinical manifestations and detection of pantothenate kinase 2 gene mutation in a patient with Hallervorden-Spatz syndrome]. 6 54
20193558 2009
32
Clinical and genetic delineation of neurodegeneration with brain iron accumulation. 61 57
18981035 2009
33
Partial deficit of pantothenate kinase 2 catalytic activity in a case of tremor-predominant neurodegeneration with brain iron accumulation. 6 61
16450344 2006
34
Atypical Hallervorden-Spatz disease with preserved cognition and obtrusive obsessions and compulsions. 6 54
15834858 2005
35
MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients. 6 61
15565311 2005
36
Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. 54 6
15659606 2005
37
Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. 57 61
15525657 2005
38
[123I]FP-CIT SPECT findings in two patients with Hallervorden-Spatz disease with homozygous mutation in PANK2 gene. 54 57
15642932 2005
39
Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic. 6 54
14638969 2003
40
Incidence of PKAN determined by bioinformatic and population-based analysis of ~140,000 humans. 57
31540697 2019
41
Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. 57
29395073 2018
42
Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports. 6
28821231 2017
43
Consensus clinical management guideline for pantothenate kinase-associated neurodegeneration (PKAN). 25 61
28034613 2017
44
Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. 6
26795593 2016
45
Pallidal neuronal apolipoprotein E in pantothenate kinase-associated neurodegeneration recapitulates ischemic injury to the globus pallidus. 25 61
26547561 2015
46
Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions. 6
26087139 2015
47
Does lesioning surgery have a role in the management of multietiological tremor in the era of Deep Brain Stimulation? 61 25
25128653 2014
48
New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. 61 25
23269600 2013
49
Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: results of a phase II pilot trial. 25 61
21557313 2011
50
The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration. 25 61
21877312 2011

Variations for Neurodegeneration with Brain Iron Accumulation 1

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

6 (show top 50) (show all 127)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PANK2 NC_000020.11:g.(?_3889081)_(3912654_?)del Deletion Pathogenic 526631 GRCh37: 20:3869728-3893301
GRCh38: 20:3889081-3912654
2 PANK2 GRCh37/hg19 20p13(chr20:3888573-3888925) copy number loss Pathogenic 813319 GRCh37: 20:3888573-3888925
GRCh38:
3 PANK2 NM_153638.4(PANK2):c.570C>G (p.Tyr190Ter) SNV Pathogenic 4549 rs137852960 GRCh37: 20:3870317-3870317
GRCh38: 20:3889670-3889670
4 PANK2 NM_024960.6(PANK2):c.-84C>T SNV Pathogenic 4550 rs137852961 GRCh37: 20:3888734-3888734
GRCh38: 20:3908087-3908087
5 PANK2 NM_024960.6(PANK2):c.-18C>T SNV Pathogenic 4551 rs137852962 GRCh37: 20:3888800-3888800
GRCh38: 20:3908153-3908153
6 PANK2 NM_024960.6(PANK2):c.539G>A (p.Ser180Asn) SNV Pathogenic 4552 rs137852963 GRCh37: 20:3893281-3893281
GRCh38: 20:3912634-3912634
7 PANK2 NM_024960.6(PANK2):c.569_571del (p.Arg190_Glu191delinsGln) Deletion Pathogenic 4560 rs766251466 GRCh37: 20:3897603-3897605
GRCh38: 20:3916956-3916958
8 PANK2 NM_024960.6(PANK2):c.-246+729C>A SNV Pathogenic 4561 rs137852969 GRCh37: 20:3870280-3870280
GRCh38: 20:3889633-3889633
9 PANK2 NM_153638.3(PANK2):c.1235+1G>T SNV Pathogenic 431115 rs1135401789 GRCh37: 20:3891478-3891478
GRCh38: 20:3910831-3910831
10 PANK2 NM_153638.3(PANK2):c.936T>A (p.Cys312Ter) SNV Pathogenic 437451 rs1555787799 GRCh37: 20:3888880-3888880
GRCh38: 20:3908233-3908233
11 PANK2 NM_001324193.2(PANK2):c.-133_-132del Deletion Pathogenic 456524 rs778550409 GRCh37: 20:3891418-3891419
GRCh38: 20:3910771-3910772
12 PANK2 NM_153638.3(PANK2):c.680A>G (p.Tyr227Cys) SNV Pathogenic 456525 rs1555787646 GRCh37: 20:3888624-3888624
GRCh38: 20:3907977-3907977
13 PANK2 NM_024960.6(PANK2):c.553_556del (p.Met185fs) Deletion Pathogenic 417619 rs1555789557 GRCh37: 20:3897587-3897590
GRCh38: 20:3916940-3916943
14 PANK2 NM_153638.3(PANK2):c.1236-2A>C SNV Pathogenic 526627 rs1261714833 GRCh37: 20:3893103-3893103
GRCh38: 20:3912456-3912456
15 PANK2 NM_001324193.2(PANK2):c.-212del Deletion Pathogenic 565372 rs753400880 GRCh37: 20:3891337-3891337
GRCh38: 20:3910690-3910690
16 PANK2 NM_001324193.2(PANK2):c.-52del Deletion Pathogenic 573171 rs1568574931 GRCh37: 20:3893120-3893120
GRCh38: 20:3912473-3912473
17 PANK2 NM_001324193.2(PANK2):c.-328+71del Deletion Pathogenic 579971 rs1568569941 GRCh37: 20:3888853-3888853
GRCh38: 20:3908206-3908206
18 PANK2 NM_153638.3(PANK2):c.1211A>T (p.Asn404Ile) SNV Pathogenic 648367 rs752078407 GRCh37: 20:3891453-3891453
GRCh38: 20:3910806-3910806
19 PANK2 NM_153638.3(PANK2):c.851_855dup (p.Arg286fs) Duplication Pathogenic 664234 rs1600534514 GRCh37: 20:3888794-3888795
GRCh38: 20:3908147-3908148
20 PANK2 NM_024960.6(PANK2):c.478C>T (p.Arg160Ter) SNV Pathogenic 667397 rs1250997630 GRCh37: 20:3893220-3893220
GRCh38: 20:3912573-3912573
21 PANK2 NM_001324193.2(PANK2):c.-224_-221del Deletion Pathogenic 807647 rs1600542260 GRCh37: 20:3891325-3891328
GRCh38: 20:3910678-3910681
22 PANK2 NM_001324193.2(PANK2):c.-223C>A SNV Pathogenic 807648 rs1600542275 GRCh37: 20:3891328-3891328
GRCh38: 20:3910681-3910681
23 PANK2 NM_153638.3(PANK2):c.573del (p.Ser191fs) Deletion Pathogenic 846245 GRCh37: 20:3870320-3870320
GRCh38: 20:3889673-3889673
24 PANK2 NM_024960.6(PANK2):c.809_828del (p.Gly270fs) Deletion Pathogenic 852118 GRCh37: 20:3903901-3903920
GRCh38: 20:3923254-3923273
25 PANK2 NM_024960.6(PANK2):c.-53_-52CT[1] Microsatellite Pathogenic 862386 GRCh37: 20:3888765-3888766
GRCh38: 20:3908118-3908119
26 PANK2 NM_153638.3(PANK2):c.445G>T (p.Glu149Ter) SNV Pathogenic 937503 GRCh37: 20:3870192-3870192
GRCh38: 20:3889545-3889545
27 PANK2 NM_153638.3(PANK2):c.1162dup (p.Val388fs) Duplication Pathogenic 945176 GRCh37: 20:3891402-3891403
GRCh38: 20:3910755-3910756
28 PANK2 NM_024960.6(PANK2):c.-246+766_-246+767del Deletion Pathogenic 803593 rs1600477446 GRCh37: 20:3870316-3870317
GRCh38: 20:3889669-3889670
29 PANK2 NM_001386393.1(PANK2):c.905+1G>C SNV Pathogenic 1030294 GRCh37: 20:3891478-3891478
GRCh38: 20:3910831-3910831
30 PANK2 NM_153638.3(PANK2):c.1561G>A (p.Gly521Arg) SNV Pathogenic 4548 rs137852959 GRCh37: 20:3899342-3899342
GRCh38: 20:3918695-3918695
31 PANK2 NM_153638.3(PANK2):c.1583C>T (p.Thr528Met) SNV Pathogenic 4556 rs137852967 GRCh37: 20:3899364-3899364
GRCh38: 20:3918717-3918717
32 PANK2 NM_024960.6(PANK2):c.540-1G>T SNV Pathogenic 4559 rs148987163 GRCh37: 20:3897573-3897573
GRCh38: 20:3916926-3916926
33 PANK2 NM_153638.3(PANK2):c.1441C>T (p.Arg481Ter) SNV Pathogenic 4557 rs137852968 GRCh37: 20:3897602-3897602
GRCh38: 20:3916955-3916955
34 PANK2 NM_001324193.2(PANK2):c.-328+92_-328+98del Deletion Pathogenic 4547 rs879253712 GRCh37: 20:3888871-3888877
GRCh38: 20:3908224-3908230
35 PANK2 NM_001324193.2(PANK2):c.-59_-58dup Duplication Pathogenic/Likely pathogenic 526628 rs1555788619 GRCh37: 20:3893118-3893119
GRCh38: 20:3912471-3912472
36 PANK2 NM_024960.6(PANK2):c.*40G>C SNV Likely pathogenic 430728 rs1131692166 GRCh37: 20:3903981-3903981
GRCh38: 20:3923334-3923334
37 PANK2 NM_153638.3(PANK2):c.1585A>G (p.Ile529Val) SNV Likely pathogenic 642654 rs761156912 GRCh37: 20:3899366-3899366
GRCh38: 20:3918719-3918719
38 PANK2 NM_024960.6(PANK2):c.608T>C (p.Leu203Ser) SNV Likely pathogenic 803595 rs111863748 GRCh37: 20:3897642-3897642
GRCh38: 20:3916995-3916995
39 PANK2 NM_024960.6(PANK2):c.-246+701_-246+708del Deletion Likely pathogenic 504213 rs755653150 GRCh37: 20:3870251-3870258
GRCh38: 20:3889604-3889611
40 PANK2 NM_153638.3(PANK2):c.1412+1G>C SNV Likely pathogenic 652533 rs1600548506 GRCh37: 20:3893282-3893282
GRCh38: 20:3912635-3912635
41 PANK2 NM_153638.3(PANK2):c.588C>G (p.Val196=) SNV Conflicting interpretations of pathogenicity 737006 rs746054643 GRCh37: 20:3870335-3870335
GRCh38: 20:3889688-3889688
42 PANK2 NM_153638.3(PANK2):c.585G>T (p.Ser195=) SNV Conflicting interpretations of pathogenicity 772588 rs375741383 GRCh37: 20:3870332-3870332
GRCh38: 20:3889685-3889685
43 PANK2 NM_001324193.2(PANK2):c.-239G>C SNV Conflicting interpretations of pathogenicity 803594 rs754521581 GRCh37: 20:3891312-3891312
GRCh38: 20:3910665-3910665
44 PANK2 NM_153638.4(PANK2):c.1213T>G (p.Tyr405Asp) SNV Conflicting interpretations of pathogenicity 995568 GRCh37: 20:3891455-3891455
GRCh38: 20:3910808-3910808
45 PANK2 NM_153638.3(PANK2):c.348G>A (p.Gly116=) SNV Conflicting interpretations of pathogenicity 720016 rs750766653 GRCh37: 20:3870095-3870095
GRCh38: 20:3889448-3889448
46 PANK2 NM_153638.3(PANK2):c.1537-3C>G SNV Uncertain significance 648878 rs370766524 GRCh37: 20:3899315-3899315
GRCh38: 20:3918668-3918668
47 PANK2 NM_153638.3(PANK2):c.37T>C (p.Trp13Arg) SNV Uncertain significance 646103 rs971003044 GRCh37: 20:3869784-3869784
GRCh38: 20:3889137-3889137
48 PANK2 NM_153638.3(PANK2):c.1593G>A (p.Met531Ile) SNV Uncertain significance 647174 rs1600571977 GRCh37: 20:3899374-3899374
GRCh38: 20:3918727-3918727
49 PANK2 NM_153638.3(PANK2):c.1340A>G (p.Asp447Gly) SNV Uncertain significance 573713 rs1568575238 GRCh37: 20:3893209-3893209
GRCh38: 20:3912562-3912562
50 PANK2 NM_153638.3(PANK2):c.1082A>G (p.Tyr361Cys) SNV Uncertain significance 575512 rs1568572918 GRCh37: 20:3891324-3891324
GRCh38: 20:3910677-3910677

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

72 (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 9.4 WDR45 VPS13A TOR1A SNCA PLA2G6 PANK4

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 9.77 PANK4 PANK3 PANK2 PANK1 COASY
2 positive regulation of exocytosis GO:0045921 9.43 SNCA PLA2G6
3 iron ion transport GO:0006826 9.4 FTL CP
4 cellular iron ion homeostasis GO:0006879 9.33 FTL CP ATP13A2
5 regulation of neuronal synaptic plasticity GO:0048168 9.32 SNCA JPH3
6 synaptic vesicle transport GO:0048489 9.26 TOR1A SNCA
7 autophagy GO:0006914 9.26 WDR45 VPS13A C19orf12 ATP13A2
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 nucleotide binding GO:0000166 9.8 TOR1A PANK4 PANK3 PANK2 PANK1 COASY
2 ATP binding GO:0005524 9.7 TOR1A PANK4 PANK3 PANK2 PANK1 COASY
3 phosphatidylinositol-3,5-bisphosphate binding GO:0080025 9.37 WDR45 ATP13A2
4 ferrous iron binding GO:0008198 9.32 SNCA FTL
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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
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41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
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50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
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71 UMLS via Orphanet
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