832 results match your criteria: "Hallervorden-Spatz Disease"
J Clin Med
August 2022
Centro della Microcitemia, delle Anemie Congenite e dei Disordini del Metabolismo del Ferro, EO Ospedali Galliera, 16128 Genoa, Italy.
Neurodegeneration with brain iron accumulation (NBIA) comprises various rare clinical entities with brain iron overload as a common feature. Magnetic resonance imaging (MRI) allows diagnosis of this condition, and genetic molecular testing can confirm the diagnosis to better understand the intracellular damage mechanism involved. NBIA groups disorders include: pantothenate kinase-associated neurodegeneration (PKAN), mutations in the gene encoding pantothenate kinase 2 (PANK2); neuroferritinopathy, mutations in the calcium-independent phospholipase A2 gene (PLA2G6); aceruloplasminemia; and other subtypes with no specific clinical or MRI specific patterns identified.
View Article and Find Full Text PDFOrphanet J Rare Dis
August 2022
Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, 41013, Sevilla, Spain.
Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA subtypes. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) that result in dysfunction in PANK2 enzyme activity, with consequent deficiency of coenzyme A (CoA) biosynthesis, as well as low levels of essential metabolic intermediates such as 4'-phosphopantetheine, a necessary cofactor for essential cytosolic and mitochondrial proteins.
View Article and Find Full Text PDFAm J Trop Med Hyg
August 2022
Department of Psychiatry, Berhampore Mental Hospital, Behrampore, West Bengal, India.
Dystonic storm (also called status dystonicus) is a neurological emergency characterized by sustained/intermittent involuntary generalized muscle contractions resulting in repetitive painful twisting movements and abnormal postures. It is commonly documented in patients with diagnosed primary dystonic syndromes or secondary dystonic states (i.e.
View Article and Find Full Text PDFJ Mov Disord
September 2022
Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Objective: To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN).
Methods: We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke- Fahn-Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected.
This case series describes the ocular and retinal manifestations of rare eye diseases in systemic syndromes. This observational case series consists of five patients with varied ophthalmic manifestations and documentation of imaging in rare pediatric and adult retinopathies. Two patients had Kearns Sayre syndrome (KSS) based on the classical triad of external ophthalmoplegia, pigmentary retinopathy, and onset before 20 years of age.
View Article and Find Full Text PDFAutophagy
October 2022
Department of Biological Sciences, Dedman College of Humanities and Sciences, Southern Methodist University, Dallas, TX, USA.
Despite certain overlapping clinical presentations, the two human neurodegenerative diseases pantothenate kinase-associated neurodegeneration (PKAN) and Parkinson disease (PD) have distinct genetic etiologies. During our work using Drosophila to study PKAN and PINK1-related PD, we found some common mitochondrial abnormalities in these two disease models, suggesting a potential link in pathogenesis between them. When we delve into their underlying mechanisms, mitochondrial quality control (MQC) stands at the crossroads.
View Article and Find Full Text PDFJ Med Case Rep
June 2022
"Pedro Diaz Coello" Policlinic, Holguin, Cuba.
Background: Type 1 neurodegeneration with brain iron accumulation is a rare neurological disorder with estimated prevalence of one to two per million persons worldwide, characterized by progressive degeneration of basal ganglia, globus pallidus, and reticular part of substantia nigra, produced by brain iron accumulation due to a defect in the gene producing pantothenate kinase 2. Clinical presentations include dystonia, dysarthria, dysphagia, dementia, severe mental retardation, and severe movement disability at later stages. The characteristic pattern on brain magnetic resonance imaging shows the "eye of the tiger" sign.
View Article and Find Full Text PDFNeurol India
May 2022
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal-recessive disease characterized by iron accumulation in the brain due to PANK2 gene mutation. The typical "eye-of-the-tiger" sign is the characteristic manifestation of brain magnetic resonance imaging (MRI). We report a Chinese patient with atypical PKAN whose brain MRI scans displayed the typical "eye-of-the-tiger" sign in bilateral pallidum.
View Article and Find Full Text PDFNat Commun
May 2022
State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Human neurodegenerative disorders often exhibit similar pathologies, suggesting a shared aetiology. Key pathological features of Parkinson's disease (PD) are also observed in other neurodegenerative diseases. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations in the human PANK2 gene, which catalyzes the initial step of de novo CoA synthesis.
View Article and Find Full Text PDFFront Aging Neurosci
April 2022
Department of Neurology, Institute of Neuroscience, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder caused by mutations in the mitochondrial pantothenate kinase 2 () gene and displays an inherited autosomal recessive pattern. In this study, we identified eight mutations, including three novel mutations (c.1103A > G/p.
View Article and Find Full Text PDFParkinsonism Relat Disord
May 2022
Department of Radiology, CEDIMAT, Plaza de la Salud, Santo Domingo, Dominican Republic. Electronic address:
Background: To examine structural connectivity of white matter tracts in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) dystonia and identify those ones which correlate negatively to severity of symptoms.
Methods: In a group of 41 patients suffering from PKAN dystonia and an age- and gender-matched control group, white matter tractography was carried out, based on diffusion tensor imaging magnetic resonance data. Postprocessing included assessment of Quantitative Anisotropy (QA) using q-space diffeomorphic reconstruction in order to reduce influence of iron accumulation in globus pallidus of patients.
World Neurosurg
July 2022
Department of Pediatrics, Peking University First Hospital, Peking University, Beijing, People's Republic of China; Department of Pediatric Surgery, Peking University First Hospital, Peking University, Beijing, People's Republic of China. Electronic address:
Objective: Dystonia in pantothenate kinase-associated neurodegeneration (PKAN) is progressive despite medication. Deep brain stimulation (DBS) was reported to effectively provide symptom relief. No consensus exists in candidate and target selection for DBS.
View Article and Find Full Text PDFOrphanet J Rare Dis
March 2022
Department of Laboratory Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Background: Neurodegeneration with brain iron accumulation describes a group of rare heterogeneous progressive neurodegenerative disorders characterized by excessive iron accumulation in the basal ganglia region. Pantothenate kinase-associated neurodegeneration (PKAN) is a major form of this disease.
Results: A total of 7 unrelated patients were diagnosed with PKAN in a single tertiary center from August 2009 to February 2018.
Neurodegeneration associated with defective pantothenate kinase-2 (PKAN) is an early-onset monogenic autosomal-recessive disorder. The hallmark of the disease is the massive accumulation of iron in the globus pallidus brain region of patients. PKAN is caused by mutations in the PANK2 gene encoding the mitochondrial enzyme pantothenate kinase-2, whose function is to catalyze the first reaction of the CoA biosynthetic pathway.
View Article and Find Full Text PDFBiomolecules
February 2022
Center for Medical Biochemistry, Max Perutz Labs, Medical University of Vienna, 1090 Vienna, Austria.
Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive neurodegenerative disease caused by mutations in the pantothenate kinase 2 (PANK2) gene and associated with iron deposition in basal ganglia. Pantothenate kinase isoforms catalyze the first step in coenzyme A (CoA) biosynthesis. Since PANK2 is the only isoform in erythrocytes, these cells are an excellent ex vivo model to study the effect of PANK2 point mutations on expression/stability and activity of the protein as well as on the downstream molecular consequences.
View Article and Find Full Text PDFJ Transl Med
February 2022
Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, USA.
Background: Pantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency.
View Article and Find Full Text PDFIran J Basic Med Sci
September 2021
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Objectives: Infantile neuroaxonal degeneration (INAD) is a rare subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders. This progressive disorder may develop during the early years of life. Affected individuals mostly manifest developmental delay and/or psychomotor regression as well as other neurological deficits.
View Article and Find Full Text PDFCan J Neurol Sci
January 2023
Department of Neurology, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Background: Neurodegeneration with brain iron accumulation (NBIA) is a rare genetic disorder. Its clinical manifestations comprise a wide spectrum mainly movement disorders. Seizure as a clinical manifestation is known to occur in some NBIAs, but the exact prevalence of epilepsy in each individual disorder is not well elucidated.
View Article and Find Full Text PDFJ Biol Chem
March 2022
Section of Infectious Diseases, Department of Internal Medicine and Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:
Pantothenate kinase-associated neurodegeneration (PKAN) is an incurable rare genetic disorder of children and young adults caused by mutations in the PANK2 gene, which encodes an enzyme critical for the biosynthesis of coenzyme A. Although PKAN affects only a small number of patients, it shares several hallmarks of more common neurodegenerative diseases of older adults such as Alzheimer's disease and Parkinson's disease. Advances in etiological understanding and treatment of PKAN could therefore have implications for our understanding of more common diseases and may shed new lights on the physiological importance of coenzyme A, a cofactor critical for the operation of various cellular metabolic processes.
View Article and Find Full Text PDFNeurocase
December 2021
Department of Neurology, Colentina Clinical Hospital, Bucharest, Romania.
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited disorders characterised by cerebral iron overload mainly in the basal ganglia. Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a form of NBIA caused by pathogenic C19orf12 gene variants. We report on a Romanian patient with MPAN confirmed through exome sequencing, revealing a homozygous nonsense variant in the C19orf12 gene, NM_001031726.
View Article and Find Full Text PDFTremor Other Hyperkinet Mov (N Y)
January 2022
Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Street Institute of Child Health, UCL, London, UK.
Background: Neurodegeneration with brain iron accumulation (NBIA) disorders comprise a group of rare but devastating inherited neurological diseases with unifying features of progressive cognitive and motor decline, and increased iron deposition in the basal ganglia. Although at present there are no proven disease-modifying treatments, the severe nature of these monogenic disorders lends to consideration of personalized medicine strategies, including targeted gene therapy. In this review we summarize the progress and future direction towards precision therapies for NBIA disorders.
View Article and Find Full Text PDFNeurol India
November 2021
Neurology Clinic, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
A disturbed iron metabolism may damage brain and trigger disorders known as neurodegeneration with brain iron accumulation (NBIA). NBIAs are rare, inherited disorders in which responsible mutations affect the function of proteins that participate in tissue iron homeostasis. Accumulated iron, which may be recognized as a low signal intensity on T2-weighted MRI images, oftentimes points to a diagnosis.
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
October 2021
Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
Neuroacanthocytosis is a group of neurodegenerative diseases manifested by a combition of neurological symptoms (most often choreic hyperkinesis) and the presence of an increased number of acanthocytes (erythrocytes with horns) in the peripheral blood. This group includes chorea-acanthocytosis, MacLeod's syndrome, pantothenate kinase-associated neurodegeneration, Huntington-like disease type 2, and some other very rare diseases. This article presents a genetically confirmed clinical case of chorea-acanthocytosis associated with a compound mutation in the VPS13A gene, discusses in detail the stages of a diagnostic search, presents an algorithm for examining patients with chorea.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
November 2021
Department of Neurology and Stereotactic Neurosurgery, Otto Von Guericke University Magdeburg, Magdeburg, Germany.
Hallervorden-Spatz disease (HSD) has been recently renamed to pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA), mainly due to the unethical behavior of Julius Hallervorden in the National Socialist (NS) euthanasia program of the Nazi Third Reich. The role of the second name giver in the NS euthanasia program is less clear. Hugo Spatz was the director of the Kaiser Wilhelm Institute for Brain Research in Berlin-Buch during World War II (WWII), renamed to Max Planck Institute after 1945.
View Article and Find Full Text PDFACS Chem Biol
November 2021
Department of Biochemistry, Stellenbosch University, Stellenbosch, 7600, South Africa.
The pantothenate analogue hopantenate (HoPan) is widely used as a modulator of coenzyme A (CoA) levels in cell biology and disease models─especially for pantothenate kinase associated neurodegeneration (PKAN), a genetic disease rooted in impaired CoA metabolism. This use of HoPan was based on reports that it inhibits pantothenate kinase (PanK), the first enzyme of CoA biosynthesis. Using a combination of enzyme kinetic studies, crystal structure analysis, and experiments in a typical PKAN cell biology model, we demonstrate that instead of inhibiting PanK, HoPan relies on it for metabolic activation.
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