Pantothenate Kinase-Associated Neurodegeneration (Hallervorden-Spatz Disease)

A rare autosomal recessive degenerative disorder which usually presents in late childhood or adolescence. Clinical manifestations include progressive MUSCLE SPASTICITY; hyperreflexia; MUSCLE RIGIDITY; DYSTONIA; DYSARTHRIA; and intellectual deterioration which progresses to severe dementia over several years. (From Adams et al., Principles of Neurology, 6th ed, p972; Davis & Robertson, Textbook of Neuropathology, 2nd ed, pp972-929)

Also Known As:

Hallervorden-Spatz Disease; Hallervorden-Spatz Syndrome; Neuroaxonal Dystrophy, Juvenile-Onset; Neurodegeneration With Brain Iron Accumulation 1; Neurodegeneration with Brain Iron Accumulation Type 1; PKAN Neuroaxonal Dystrophy, Juvenile-Onset; Pigmentary Pallidal Atrophy; Degeneration, Pigmentary Pallidal; Dystrophies, Juvenile-Onset Neuroaxonal; Dystrophy, Juvenile-Onset Neuroaxonal; Hallervorden Spatz Disease; Hallervorden Spatz Syndrome; Juvenile-Onset Neuroaxonal Dystrophies; Juvenile-Onset Neuroaxonal Dystrophy; Neuroaxonal Dystrophies, Juvenile-Onset; Neuroaxonal Dystrophy, Juvenile Onset; Neurodegeneration, Pantothenate Kinase-Associated; PKAN Neuroaxonal Dystrophy, Juvenile Onset; Pallidal Atrophy, Pigmentary; Pantothenate Kinase Associated Neurodegeneration; Pigmentary Pallidal Degeneration

Networked: 301 relevant articles (4 outcomes, 15 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Parkinson Disease (Parkinson's Disease)
2.	Huntington Disease (Huntington's Disease)
3.	Dystonia (Limb Dystonia)
4.	Alzheimer Disease (Alzheimer's Disease)
5.	Multiple System Atrophy

Experts

1.	Hayflick, Susan J: 15 articles (12/2021 - 01/2003)
2.	Klopstock, Thomas: 9 articles (01/2022 - 05/2005)
3.	Tiranti, Valeria: 9 articles (12/2020 - 03/2012)
4.	Hayflick, S J: 9 articles (03/2018 - 08/2001)
5.	Gregory, Allison: 8 articles (12/2021 - 01/2005)
6.	Hogarth, Penelope: 8 articles (12/2021 - 11/2013)
7.	Hayflick, Susan: 7 articles (01/2022 - 04/2010)
8.	Schneider, Susanne A: 7 articles (01/2021 - 09/2010)
9.	Levi, Sonia: 7 articles (12/2020 - 12/2010)
10.	Garavaglia, Barbara: 7 articles (10/2016 - 12/2010)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pantothenate Kinase-Associated Neurodegeneration:

1.	DeferiproneIBA 01/01/2019 - "Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study." 12/11/2017 - "A pilot trial of deferiprone in pantothenate kinase-associated neurodegeneration patients." 06/01/2014 - "Efficacy and safety of deferiprone for the treatment of pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA): results from a four years follow-up." 11/01/2011 - "Four patients with genetically-confirmed pantothenate kinase-associated neurodegeneration, and 2 with parkinsonism and focal dystonia, but inconclusive genetic tests, received 15 mg/kg deferiprone bid. " 08/01/2011 - "Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: results of a phase II pilot trial."
2.	IronIBA 12/01/2020 - "The aim of this study was to look for deviations of cerebral perfusion in patients suffering from pantothenate kinase-associated neurodegeneration, where the globus pallidus is affected by severe accumulation of iron. " 03/01/2018 - "The aim of this study was to determine the morphologic spectrum of the "eye-of-the-tiger" sign and the topographic pattern of iron deposition in a group of patients with pantothenate kinase-associated neurodegeneration. " 06/01/2023 - "The "eye-of-the-tiger" sign in brain magnetic resonance imaging (MRI) is typically associated with neurodegeneration with brain iron accumulation disorders, especially pantothenate kinase-associated neurodegeneration. " 01/01/2023 - "Pantothenate kinase-associated neurodegeneration (PKAN) is the most common "Neurodegeneration with Brain Iron Accumulation" disorder. " 03/01/2022 - "Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal-recessive disease characterized by iron accumulation in the brain due to PANK2 gene mutation. "
3.	pantethineIBA 01/01/2020 - "This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN). " 01/01/2020 - "Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study." 01/01/2014 - "We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. " 04/13/2010 - "Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration." 01/01/2014 - "Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model."
4.	Chelating AgentsIBA 11/20/2023 - "The use of iron chelators has been successful in the treatment of diseases such as transfusion-dependent thalassemia and pantothenate kinase-associated neurodegeneration. " 08/01/2011 - "The safety and efficacy of the oral iron-chelating agent deferiprone on magnetic resonance pallida iron concentration and on clinical status were investigated in 10 patients affected by pantothenate kinase-associated neurodegeneration. "
5.	Type A Botulinum Toxins (Botox)FDA Link 05/16/2011 - "Efficacy of botulinum toxin A treatment in a case of pantothenate kinase associated neurodegeneration (PKAN)."
6.	pantothenate kinaseIBA 04/01/2005 - "To study pantothenate kinase 2 (PANK2) gene mutations in Chinese patients with Hallervorden-Spatz syndrome (HSS). " 01/01/2022 - "Genetic mutation spectrum of pantothenate kinase-associated neurodegeneration expanded by breakpoint sequencing in pantothenate kinase 2 gene." 03/01/2017 - "Pantothenate kinase-associated neurodegeneration (PKAN) is caused by mutations of the pantothenate kinase 2 (PANK2) gene. " 04/01/2016 - "The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. " 01/01/2016 - "Pantothenate-kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder caused by mutations in the pantothenate kinase 2 (PANK2) gene. "
7.	Coenzyme A (CoA)IBA 11/01/2022 - "Studies aimed at supporting different treatment approaches for pantothenate kinase-associated neurodegeneration (PKAN) have revealed the complexity of coenzyme A (CoA) metabolism and the limits of our current knowledge about disease pathogenesis. " 10/24/2023 - "BBP-671 crosses the blood brain barrier to correct the neuron-specific CoA deficiency and improve motor function in a mouse model of pantothenate kinase associated neurodegeneration. " 01/01/2022 - "Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations in the human PANK2 gene, which catalyzes the initial step of de novo CoA synthesis. " 01/01/2015 - "Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice." 02/01/2009 - "Mutations in the PANK2 gene account for the majority of NBIA cases and cause an autosomal recessive inborn error of coenzyme A metabolism called pantothenate kinase associated neurodegeneration (PKAN). "
8.	Proteins (Proteins, Gene)FDA Link 01/01/2021 - "Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives." 01/01/2021 - "The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. " 01/01/2023 - "The PANK2 gene, which encodes mitochondrial pantothenate kinase 2 protein, is the disease-causing gene for pantothenate kinase-associated neurodegeneration (PKAN). " 09/01/2021 - "Among NBIAs, the most common is pantothenate kinase-associated neurodegeneration (PKAN-NBIA 1) (30%-50% of all NBIA cases), that occurrs as a consequence of the autosomal recessive mutation in PANK2 gene, followed by phospholipase 2-associated neurodegeneration (PLAN, NBIA 2), due to mutation in PLA2G6 gene, and mitochondrial membrane protein-associated neurodegeneration (MPAN) with the underlying C19orf12 mutation [Table 1]. " 01/01/2021 - "The four most common forms are pantothenate kinase-associated neurodegeneration (PKAN), phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN), beta-propeller protein-associated neurodegeneration (BPAN) and mitochondrial membrane protein-associated neurodegeneration (MPAN). "
9.	Familial apoceruloplasmin deficiencyIBA 12/01/2016 - "However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease." 03/01/2017 - "In this case series, we present 4 genetically proven cases of NBIA (including neuroferritinopathy, pantothenate-kinase-associated neurodegeneration, and aceruloplasminemia) with late disease onset, which resembled isolated adult-onset craniocervical dystonia at disease onset. " 04/29/2008 - "The known causes of NBIA include pantothenate kinase-associated neurodegeneration (PKAN), neuroferritinopathy, infantile neuroaxonal dystrophy (INAD), and aceruloplasminemia. " 01/01/2013 - "For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. " 12/01/2014 - "Neuroimaging, detected metal deposits in central nervous system (CNS) but not in peripheral organs, while serum analysis excluded pantothenate-kinase associated neurodegeneration and aceruloplasminemia. "
10.	Baclofen FDA LinkGeneric 05/01/2004 - "Status dystonicus and Hallervorden-Spatz disease: treatment with intrathecal baclofen and pallidotomy." 04/01/2004 - "Seven children (aged 2-16 years) with dystonia of various aetiologies (dyskinetic cerebral palsy, pantothenate kinase-associated neurodegeneration and Aicardi-Goutières syndrome) underwent transcranial magnetic stimulation, H-reflex and flexor reflex studies before and after intrathecal injection of baclofen. " 08/01/2013 - "Treatment of classic pantothenate kinase-associated neurodegeneration with deferiprone and intrathecal baclofen."

Therapies and Procedures

1.	Ketogenic Diet 01/01/2014 - "Only Pank2(-/-) mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. " 01/01/2014 - "Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model."
2.	Deep Brain Stimulation 04/01/2012 - "The purpose of this study was to evaluate the mutation status of PANK2 among Korean patients with pantothenate kinase-associated neurodegeneration (PKAN) and to document the outcome of pallidal deep brain stimulation (DBS). " 09/01/2022 - "To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN). " 04/01/2019 - "Amelioration of Dystonic Opisthotonus in Pantothenate Kinase-Associated Neurodegeneration Syndrome with Absent "Eye-of-the-Tiger" Sign Following Bilateral Pallidal Deep Brain Stimulation." 01/01/2019 - "Deep brain stimulation for pantothenate kinase-associated neurodegeneration: A meta-analysis." 01/01/2016 - "Deep brain stimulation in the globus pallidus compensates response inhibition deficits: evidence from pantothenate kinase-associated neurodegeneration."
3.	Therapeutics 01/01/2022 - "Redesigning therapies for pantothenate kinase-associated neurodegeneration." 01/01/2021 - "Rational Design of Novel Therapies for Pantothenate Kinase-Associated Neurodegeneration." 01/01/2019 - "Proposed Therapies for Pantothenate-Kinase-Associated Neurodegeneration." 01/01/2019 - "The goal of such measures in patients with pantothenate kinase-associated neurodegeneration is to facilitate development of disease-modifying therapeutics in multiple drug development programs." 01/01/2019 - "Dental appliance therapy in pantothenate kinase-associated neurodegeneration: Case report."
4.	Activities of Daily Living (ADL) 01/01/2019 - "A clinimetric study of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale conducted in patients with pantothenate kinase-associated neurodegeneration or their caregivers (N = 40 at first assessment; N = 39 at second assessment) demonstrated high content and construct validity and excellent test-retest reliability over an approximately 2-week period. " 01/01/2019 - "The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale was developed to assess activities of daily living related to motor functioning in patients with pantothenate kinase-associated neurodegeneration to evaluate clinically meaningful change as the primary efficacy endpoint in clinical trials. " 02/01/2019 - "Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12-item Pantothenate Kinase-Associated Neurodegeneration Activities of Daily Living (PKAN-ADL). " 02/01/2019 - "A Scale to Assess Activities of Daily Living in Pantothenate Kinase-Associated Neurodegeneration." 01/01/2019 - "The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale was developed to be broadly useful within clinical and research settings in the examination of patient response to pantothenate kinase-associated neurodegeneration therapies. "
5.	Transcranial Magnetic Stimulation 04/01/2004 - "Seven children (aged 2-16 years) with dystonia of various aetiologies (dyskinetic cerebral palsy, pantothenate kinase-associated neurodegeneration and Aicardi-Goutières syndrome) underwent transcranial magnetic stimulation, H-reflex and flexor reflex studies before and after intrathecal injection of baclofen. "