MCID: KFR001
MIFTS: 42

Kufor-Rakeb Syndrome

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

Aliases & Classifications for Kufor-Rakeb Syndrome

MalaCards integrated aliases for Kufor-Rakeb Syndrome:

Name: Kufor-Rakeb Syndrome 53 12 72 55 71 41 14 69
Parkinson Disease 9 71 28 13
Park9 53 55 71
Pallidopyramidal Degeneration with Supranuclear Upgaze Paresis and Dementia 53 71
Krppd 53 71
Krs 53 71
Pallidopyramidal Degeneration with Supranuclear Upgaze Paresis and Dementia; Krppd 53
Parkinson Disease 9, Autosomal Recessive, Juvenile-Onset; Park9 53
Parkinson Disease 9, Autosomal Recessive, Juvenile-Onset 53
Autosomal Recessive Juvenile Onset Parkinson Disease 9 12
Autosomal Recessive Parkinson Disease 9 12
Parkinson Disease Autosomal Recessive 9 71

Characteristics:

Orphanet epidemiological data:

55
kufor-rakeb syndrome
Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: adult;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
variable neurologic phenotype
average age of onset 13 years
rapidly progressive (6-24 months)
rapidly progressive (6-24 months) (in some patients)
favorable initial response to l-dopa
therapy-induced dyskinesias


HPO:

31
kufor-rakeb syndrome:
Onset and clinical course rapidly progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Kufor-Rakeb Syndrome

OMIM : 53 Kufor-Rakeb syndrome is a rare autosomal recessive form of juvenile-onset atypical Parkinson disease (PARK9) associated with supranuclear gaze palsy, spasticity, and dementia. Some patients have neuroradiologic evidence of iron deposition in the basal ganglia, indicating that the pathogenesis of PARK9 can be considered among the syndromes of neurodegeneration with brain iron accumulation (NBIA; see 234200) (summary by Bruggemann et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600. Biallelic mutation in the ATP13A2 gene also causes autosomal recessive spastic paraplegia-78 (SPG78; 617225), an adult-onset neurodegenerative disorder with overlapping features. Patients with SPG78 have later onset and prominent spasticity, but rarely parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017). (606693)

MalaCards based summary : Kufor-Rakeb Syndrome, also known as parkinson disease 9, is related to neurodegeneration with brain iron accumulation 1 and parkinson disease type 9, and has symptoms including ataxia, seizures and myoclonus. An important gene associated with Kufor-Rakeb Syndrome is ATP13A2 (ATPase 13A2), and among its related pathways/superpathways is Pantothenate and CoA biosynthesis. Affiliated tissues include brain and eye.

UniProtKB/Swiss-Prot : 71 Kufor-Rakeb syndrome: A rare form of autosomal recessive juvenile or early-onset, levodopa- responsive parkinsonism. In addition to typical parkinsonian signs, clinical manifestations of Kufor-Rakeb syndrome include behavioral problems, facial tremor, pyramidal tract dysfunction, supranuclear gaze palsy, and dementia.

Disease Ontology : 12 A disease that is characterized by supranuclear gaze palsy, spasticity, and dementia and has material basis in homozygous or compound heterozygous mutation in a lysosomal type 5 ATPase encoding gene (ATP13A2) on chromosome 1p36.

Related Diseases for Kufor-Rakeb Syndrome

Graphical network of the top 20 diseases related to Kufor-Rakeb Syndrome:



Diseases related to Kufor-Rakeb Syndrome

Symptoms & Phenotypes for Kufor-Rakeb Syndrome

Symptoms via clinical synopsis from OMIM:

53
NeurologicCentralNervousSystem:
ataxia
myoclonus
tremor
dystonia
dysarthria
more
HeadAndNeckNose:
anosmia
hyposmia

HeadAndNeckFace:
mask-like facies

NeurologicPeripheralNervousSystem:
distal sensory impairment (in some patients)
axonal sensorimotor peripheral neuropathy (in some patients)

HeadAndNeckNeck:
torticollis

NeurologicBehavioralPsychiatricManifestations:
hallucinations
psychotic episodes
aggression

HeadAndNeckEyes:
supranuclear gaze palsy
slow saccades
oculogyric dystonic spasms

LaboratoryAbnormalities:
cytoplasmic lamellar inclusions consistent with neuronal ceroid lipofuscinosis (in 1 family studied)


Clinical features from OMIM:

606693

Human phenotypes related to Kufor-Rakeb Syndrome:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 seizures 31 occasional (7.5%) HP:0001250
3 myoclonus 31 HP:0001336
4 tremor 31 HP:0001337
5 torticollis 31 HP:0000473
6 paraparesis 31 HP:0002385
7 anosmia 31 HP:0000458
8 hyposmia 31 HP:0004409
9 dysarthria 31 HP:0001260
10 gait disturbance 31 HP:0001288
11 hyperreflexia 31 HP:0001347
12 hallucinations 31 HP:0000738
13 babinski sign 31 HP:0003487
14 mask-like facies 31 HP:0000298
15 psychotic episodes 31 HP:0000725
16 rigidity 31 HP:0002063
17 dementia 31 HP:0000726
18 aggressive behavior 31 HP:0000718
19 spastic paraplegia 31 HP:0001258
20 hypokinesia 31 HP:0002375
21 parkinsonism 31 HP:0001300
22 anarthria 31 HP:0002425
23 supranuclear gaze palsy 31 HP:0000605
24 postural instability 31 HP:0002172
25 slow saccadic eye movements 31 HP:0000514
26 distal sensory impairment 31 occasional (7.5%) HP:0002936
27 akinesia 31 HP:0002304
28 parkinsonism with favorable response to dopaminergic medication 31 HP:0002548

UMLS symptoms related to Kufor-Rakeb Syndrome:


hyposmia, abnormality of extrapyramidal motor function, abnormal pyramidal signs, tremor, torticollis, myoclonus, muscle rigidity, ataxia

Drugs & Therapeutics for Kufor-Rakeb Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic Study in Young Onset Parkinson's Disease Unknown status NCT01529970

Search NIH Clinical Center for Kufor-Rakeb Syndrome

Cochrane evidence based reviews: kufor-rakeb syndrome

Genetic Tests for Kufor-Rakeb Syndrome

Genetic tests related to Kufor-Rakeb Syndrome:

# Genetic test Affiliating Genes
1 Parkinson Disease 9 28 ATP13A2

Anatomical Context for Kufor-Rakeb Syndrome

MalaCards organs/tissues related to Kufor-Rakeb Syndrome:

38
Brain, Eye

Publications for Kufor-Rakeb Syndrome

Articles related to Kufor-Rakeb Syndrome:

(show all 11)
# Title Authors Year
1
Loss of ATP13A2 impairs glycolytic function in Kufor-Rakeb syndrome patient-derived cell models. ( 27039055 )
2016
2
Poster 298 Ataxia and Dysarthria in Two Siblings with Kufor-Rakeb Syndrome: A Case Report. ( 27673054 )
2016
3
Electron-dense lamellated inclusions in 2 siblings with Kufor-Rakeb syndrome. ( 23630171 )
2013
4
Altered apoptosis regulation in Kufor-Rakeb syndrome patients with mutations in the ATP13A2 gene. ( 22117566 )
2012
5
ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome. ( 22296644 )
2012
6
Novel mutation in ATP13A2 widens the spectrum of Kufor-Rakeb syndrome (PARK9). ( 21696388 )
2012
7
Regulation of intracellular manganese homeostasis by Kufor-Rakeb syndrome-associated ATP13A2 protein. ( 21724849 )
2011
8
Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9) causing Kufor-Rakeb syndrome, a form of early-onset parkinsonism. ( 21542062 )
2011
9
Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. ( 20683840 )
2010
10
Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36. ( 11584046 )
2001
11
Pallido-pyramidal degeneration, supranuclear upgaze paresis and dementia: Kufor-Rakeb syndrome. ( 8085432 )
1994

Variations for Kufor-Rakeb Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Kufor-Rakeb Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 ATP13A2 p.Thr12Met VAR_058451 rs151117874
2 ATP13A2 p.Gly504Arg VAR_058455 rs121918227
3 ATP13A2 p.Gly533Arg VAR_058456
4 ATP13A2 p.Ala746Thr VAR_058458 rs147277743
5 ATP13A2 p.Phe182Leu VAR_066019
6 ATP13A2 p.Gly877Arg VAR_066020 rs144701072
7 ATP13A2 p.Leu1059Arg VAR_066021 rs137853967
8 ATP13A2 p.Met854Arg VAR_070194 rs587777053

ClinVar genetic disease variations for Kufor-Rakeb Syndrome:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 ATP13A2 NM_022089.3(ATP13A2): c.1101_1102dupGA (p.Thr368Argfs) duplication Pathogenic rs762033589 GRCh37 Chromosome 1, 17323608: 17323609
2 ATP13A2 NM_022089.3(ATP13A2): c.2552_2553delTT (p.Phe851Cysfs) deletion Pathogenic rs587776890 GRCh37 Chromosome 1, 17316242: 17316243
3 ATP13A2 NM_022089.3(ATP13A2): c.2561T> G (p.Met854Arg) single nucleotide variant Pathogenic rs587777053 GRCh37 Chromosome 1, 17316234: 17316234
4 ATP13A2 NM_022089.3(ATP13A2): c.2629G> A (p.Gly877Arg) single nucleotide variant Pathogenic rs144701072 GRCh37 Chromosome 1, 17314950: 17314950
5 ATP13A2 NM_022089.3(ATP13A2): c.490C> T (p.Arg164Trp) single nucleotide variant Pathogenic rs199624796 GRCh37 Chromosome 1, 17330894: 17330894
6 ATP13A2 ATP13A2, 1-BP DEL, 3057C deletion Pathogenic
7 ATP13A2 NM_022089.3(ATP13A2): c.1306+5G> A single nucleotide variant Pathogenic rs786205056 GRCh37 Chromosome 1, 17322876: 17322876
8 ATP13A2 ATP13A2, 22-BP DUP duplication Pathogenic
9 ATP13A2 NM_022089.3(ATP13A2): c.1510G> C (p.Gly504Arg) single nucleotide variant Pathogenic rs121918227 GRCh37 Chromosome 1, 17322503: 17322503
10 ATP13A2 NM_022089.3(ATP13A2): c.943G> A (p.Gly315Arg) single nucleotide variant Likely pathogenic rs150519745 GRCh37 Chromosome 1, 17326602: 17326602
11 ATP13A2 NM_022089.3(ATP13A2): c.348-9_351del deletion Pathogenic rs749798211 GRCh37 Chromosome 1, 17331313: 17331325
12 ATP13A2 NM_022089.3(ATP13A2): c.3057delC (p.Tyr1020Thrfs) deletion Pathogenic rs765632065 GRCh37 Chromosome 1, 17313567: 17313567
13 ATP13A2 NM_022089.3(ATP13A2): c.1903C> T (p.Gln635Ter) single nucleotide variant Pathogenic rs773246271 GRCh37 Chromosome 1, 17318840: 17318840

Expression for Kufor-Rakeb Syndrome

Search GEO for disease gene expression data for Kufor-Rakeb Syndrome.

Pathways for Kufor-Rakeb Syndrome

Pathways related to Kufor-Rakeb Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.9 COASY PANK2

GO Terms for Kufor-Rakeb Syndrome

Cellular components related to Kufor-Rakeb Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 8.92 COASY FBXO7 PANK2 PLA2G6

Biological processes related to Kufor-Rakeb Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium ion transmembrane transport GO:0070588 9.4 ATP13A2 ATP13A5
2 cellular calcium ion homeostasis GO:0006874 9.37 ATP13A2 ATP13A5
3 cation transport GO:0006812 9.32 ATP13A2 ATP13A5
4 negative regulation of neuron death GO:1901215 9.26 ATP13A2 FBXO7
5 ATP hydrolysis coupled cation transmembrane transport GO:0099132 9.16 ATP13A2 ATP13A5
6 coenzyme A biosynthetic process GO:0015937 8.96 COASY PANK2
7 coenzyme biosynthetic process GO:0009108 8.62 COASY PANK2

Molecular functions related to Kufor-Rakeb Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.46 ATP13A2 ATP13A5 COASY PANK2
2 calcium-transporting ATPase activity GO:0005388 8.96 ATP13A2 ATP13A5
3 cation-transporting ATPase activity GO:0019829 8.62 ATP13A2 ATP13A5

Sources for Kufor-Rakeb Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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