Kufor-Rakeb syndrome

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. Mutations in the ATP13A2 gene have been identified. OMIM: 606693

Also Known As:

Networked: 34 relevant articles (2 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Parkinsonian Disorders (Parkinsonism)
2.	Parkinson Disease (Parkinson's Disease)
3.	Dementia (Dementias)
4.	Neurodegenerative Diseases (Neurodegenerative Disease)
5.	Neuronal Ceroid-Lipofuscinoses (Neuronal Ceroid Lipofuscinosis)

Experts

1.	Krainc, Dimitri: 5 articles (05/2013 - 08/2011)
2.	Martin, Shaun: 4 articles (03/2021 - 07/2015)
3.	Vangheluwe, Peter: 4 articles (03/2021 - 07/2015)
4.	van Veen, Sarah: 4 articles (03/2021 - 07/2015)
5.	Baekelandt, Veerle: 3 articles (03/2021 - 07/2015)
6.	Holemans, Tine: 3 articles (01/2017 - 07/2015)
7.	Usenovic, Marija: 3 articles (09/2012 - 03/2012)
8.	Stiller, Barbara: 3 articles (08/2011 - 10/2006)
9.	Van den Haute, Chris: 2 articles (03/2021 - 07/2015)
10.	Agostinis, Patrizia: 2 articles (01/2016 - 07/2015)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Kufor-Rakeb syndrome:

1.	Adenosine Triphosphatases (ATPase)IBA 11/01/2015 - "The present study also establishes that G2019S mutation leads to a reduction in lysosomal pH and increased expression of the lysosomal ATPase ATP13A2, a gene linked to a parkinsonian syndrome (Kufor-Rakeb syndrome), in brain samples from mouse and human LRRK2 G2019S carriers. " 01/01/2023 - "Mutations in the human ATP13A2 (PARK9), a lysosomal ATPase, cause Kufor-Rakeb Syndrome, an early-onset form of Parkinson's disease (PD). " 01/01/2018 - "Inactivation of ATP13A2, one of the four human P5B ATPases, leads to early-onset Parkinson's disease (Kufor-Rakeb Syndrome). " 01/01/2014 - "Mutations in the ATPase 13A2 gene were found to be the causes for the Kufor-Rakeb syndrome, a rare form of recessively inherited atypical juvenile parkinsonism. " 07/21/2015 - "ATP13A2 is a lysosomal P-type transport ATPase that has been implicated in Kufor-Rakeb syndrome and Parkinson's disease (PD), providing protection against α-synuclein, Mn(2+), and Zn(2+) toxicity in various model systems. "
2.	Heavy MetalsIBA 05/29/2009 - "Further studies on the function of Ypk9p/ATP13A2 may help to define the molecular basis of Kufor-Rakeb syndrome and provide a potential link to environmental factors such as heavy metals contributing to some forms of Parkinsonism."
3.	SynucleinsIBA 03/21/2012 - "Our findings implicate lysosomal dysfunction in the pathogenesis of Kufor-Rakeb syndrome and suggest that upregulation of lysosomal function and downregulation of α-synuclein represent important therapeutic strategies for this disorder." 07/21/2015 - "ATP13A2 is a lysosomal P-type transport ATPase that has been implicated in Kufor-Rakeb syndrome and Parkinson's disease (PD), providing protection against α-synuclein, Mn(2+), and Zn(2+) toxicity in various model systems. "
4.	Proteins (Proteins, Gene)FDA Link 08/31/2023 - "Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. " 11/01/2021 - "We had 2 cases each of Mitochondrial membrane-associated neurodegeneration (MPAN) and Beta-propeller protein- associated neurodegeneration (BPAN) and 1 case of Kufor-Rakeb Syndrome (KRS). " 01/01/2013 - "This protein was initially linked to Kufor-Rakeb syndrome where it is absent or mutated. " 09/01/2012 - "Loss-of-function mutations in a lysosomal protein, ATP13A2 (PARK9), cause Kufor-Rakeb syndrome that is characterized by early-onset parkinsonism, pyramidal degeneration and dementia. " 06/01/2012 - "One of these disorders is Kufor-Rakeb syndrome, caused by mutations in the lysosomal protein ATP13A2/PARK9 and characterized by early-onset Parkinsonism, pyramidal degeneration and dementia. "
5.	P-type ATPasesIBA 11/01/2017 - "ATP13A2, which encodes a lysosomal P-type ATPase, has been identified as the causative gene for Kufor-Rakeb syndrome. " 05/15/2013 - "Mutations in ATP13A2 (PARK9), encoding a lysosomal P-type ATPase, are associated with both Kufor-Rakeb syndrome (KRS) and neuronal ceroid lipofuscinosis (NCL). " 08/01/2011 - "Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9) causing Kufor-Rakeb syndrome, a form of early-onset parkinsonism." 01/01/2016 - "The late endo-/lysosomal P-type ATPase ATP13A2 (PARK9) is implicated in Parkinson's disease (PD) and Kufor-Rakeb syndrome, early-onset atypical Parkinsonism. " 10/01/2006 - "Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). "
6.	Levodopa (L Dopa)FDA LinkGeneric 01/01/2014 - "Such mutations in ATP13A2, also named PARK9, were first identified in 2006 in a Chilean family and are associated with a juvenile-onset, levodopa-responsive type of Parkinsonism called Kufor-Rakeb syndrome (KRS). " 08/01/2012 - "ATP13A2 mutations are responsible for Kufor-Rakeb syndrome (KRS), a rare autosomal recessive juvenile parkinsonism characterized by the subacute onset of extrapyramidal, pyramidal and cognitive dysfunction with secondary nonresponsiveness to levodopa. " 09/05/2000 - "29 patients with Parkinson disease (9 with sympathetic neurocirculatory failure, 10 who had stopped receiving or had never been treated with L-dopa), 24 patients with multiple-system atrophy (17 with sympathetic neurocirculatory failure, 8 receiving L-dopa), 7 patients with pure autonomic failure, 33 controls with episodic or persistent orthostatic intolerance without sympathetic neurocirculatory failure, and 19 normal volunteers. " 08/01/2011 - "Kufor-Rakeb syndrome (KRS) is a rare form of autosomal recessive juvenile or early-onset, levodopa responsive parkinsonism and has been associated with mutations in ATP13A2(also known as PARK9), a lysosomal type 5 P-type ATPase. "
7.	ManganeseIBA 08/26/2011 - "Regulation of intracellular manganese homeostasis by Kufor-Rakeb syndrome-associated ATP13A2 protein." 01/01/2019 - "Then, due to the established connection between manganese cations and neurodegeneration, the Kufor-Rakeb syndrome and prion-related diseases are finally presented."
8.	Phospholipases A2 (Phospholipase A2)IBA 07/01/2016 - "The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. "
9.	Lysosomal Membrane ProteinsIBA 03/21/2012 - "Mutations in lysosomal membrane protein ATP13A2 (PARK9) cause familial Kufor-Rakeb syndrome characterized by early-onset parkinsonism, pyramidal degeneration and dementia. "
10.	Mutant Proteins (Protein, Mutant)IBA 01/01/2017 - "Our biochemical and immunocytochemical experiments in COS-1 and HeLa cells and patient-derived fibroblasts demonstrated that the hereditary spastic paraplegia-associated mutations, similarly to the ones causing Kufor-Rakeb syndrome and neuronal ceroid lipofuscinosis, cause loss of ATP13A2 function due to transcript or protein instability and abnormal intracellular localization of the mutant proteins, ultimately impairing the lysosomal and mitochondrial function. "

Therapies and Procedures

1.	Transcranial Magnetic Stimulation 06/01/2012 - "To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). "
2.	Deep Brain Stimulation 10/01/2022 - "Kufor Rakeb Syndrome with Novel Mutation and the Role of Deep Brain Stimulation."