776 results match your criteria Hallervorden-Spatz Disease

Type 1 neurodegeneration with brain iron accumulation: a case report.

J Med Case Rep 2022 Jun 3;16(1):217. Epub 2022 Jun 3.

"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. Read More

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Novel Compound Heterozygous Mutation in PANK2 in a Patient with an Atypical Form of Pantothenate Kinase Associated Neurodegeneration and His Family.

Neurol India 2022 Mar-Apr;70(2):737-739

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. Read More

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Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism.

Nat Commun 2022 05 3;13(1):2412. Epub 2022 May 3.

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. Read More

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Novel Mutations in Patients With Pantothenate Kinase-Associated Neurodegeneration and the Genotype-Phenotype Correlation.

Front Aging Neurosci 2022 6;14:848919. Epub 2022 Apr 6.

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. Read More

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Cerebral and cerebellar white matter tract alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

Parkinsonism Relat Disord 2022 05 4;98:1-6. Epub 2022 Apr 4.

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. Read More

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Deep Brain Stimulation (DBS) with Subthalamic Nucleus (STN) as Target for Pediatric Patients with PKAN.

World Neurosurg 2022 Jul 1;163:e317-e322. Epub 2022 Apr 1.

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. Read More

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Genetic mutation spectrum of pantothenate kinase-associated neurodegeneration expanded by breakpoint sequencing in pantothenate kinase 2 gene.

Orphanet J Rare Dis 2022 03 4;17(1):111. Epub 2022 Mar 4.

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. Read More

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Massive iron accumulation in PKAN-derived neurons and astrocytes: light on the human pathological phenotype.

Cell Death Dis 2022 02 25;13(2):185. Epub 2022 Feb 25.

IRCCS San Raffaele Scientific Institute, Milan, Italy.

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. Read More

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February 2022

A Potential Citrate Shunt in Erythrocytes of PKAN Patients Caused by Mutations in Pantothenate Kinase 2.

Biomolecules 2022 02 18;12(2). Epub 2022 Feb 18.

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. Read More

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February 2022

Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency.

J Transl Med 2022 02 23;20(1):103. Epub 2022 Feb 23.

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. Read More

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February 2022

PLA2G6 gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran.

Iran J Basic Med Sci 2021 Sep;24(9):1190-1195

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. Read More

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September 2021

Redesigning therapies for pantothenate kinase-associated neurodegeneration.

J Biol Chem 2022 03 15;298(3):101577. Epub 2022 Jan 15.

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. Read More

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Novel C19orf12 loss-of-function variant leading to neurodegeneration with brain iron accumulation.

Neurocase 2021 12 4;27(6):481-483. Epub 2022 Jan 4.

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. Read More

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December 2021

Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation.

Tremor Other Hyperkinet Mov (N Y) 2021 24;11:51. Epub 2021 Nov 24.

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. Read More

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January 2022

NBIA Syndromes: A Step Forward from the Previous Knowledge.

Neurol India 2021 Sep-Oct;69(5):1380-1388

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. Read More

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November 2021

[Case-report of neuroacanthocytosis associated with a compound mutation in the VPS13A gene].

Zh Nevrol Psikhiatr Im S S Korsakova 2021 ;121(9):104-110

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. Read More

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October 2021

Renaming of Hallervorden-Spatz disease: the second man behind the name of the disease.

J Neural Transm (Vienna) 2021 11 16;128(11):1635-1640. Epub 2021 Oct 16.

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. Read More

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November 2021

The Coenzyme A Level Modulator Hopantenate (HoPan) Inhibits Phosphopantotenoylcysteine Synthetase Activity.

ACS Chem Biol 2021 11 28;16(11):2401-2414. Epub 2021 Sep 28.

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. Read More

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November 2021

Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions.

Int J Mol Sci 2021 Jul 22;22(15). Epub 2021 Jul 22.

Department of Early Arthritis, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland.

Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. Read More

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Consensus clinical management guideline for beta-propeller protein-associated neurodegeneration.

Dev Med Child Neurol 2021 12 4;63(12):1402-1409. Epub 2021 Aug 4.

Departments of Molecular and Medical Genetics, Pediatrics, and Neurology, Oregon Health & Science University, Portland, OR, USA.

This review provides recommendations for the evaluation and management of individuals with beta-propeller protein-associated neurodegeneration (BPAN). BPAN is one of several neurodegenerative disorders with brain iron accumulation along with pantothenate kinase-associated neurodegeneration, PLA2G6-associated neurodegeneration, mitochondrial membrane protein-associated neurodegeneration, fatty acid hydroxylase-associated neurodegeneration, and COASY protein-associated neurodegeneration. BPAN typically presents with global developmental delay and epilepsy in childhood, which is followed by the onset of dystonia and parkinsonism in mid-adolescence or adulthood. Read More

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December 2021

Atypical pantothenate kinase-associated neurodegeneration with variable phenotypes in an Egyptian family.

Heliyon 2021 Jul 2;7(7):e07469. Epub 2021 Jul 2.

Institute of Global Health and Human Ecology, American University in Cairo (AUC), Cairo, Egypt.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare hereditary neurodegenerative disease characterized by an accumulation of iron within the brain. In the present report, we describe a family with 4 affected siblings presenting with variable clinical manifestations, e.g. Read More

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Neurodegeneration with brain iron accumulation: Characterization of clinical, radiological, and genetic features of pediatric patients from Southern India.

Brain Dev 2021 Nov 14;43(10):1013-1022. Epub 2021 Jul 14.

Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.

Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of rare inherited neurodegenerative disorders. Ten types of NBIA are known. Studies reporting various NBIA subtypes together are few. Read More

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November 2021

Characterization of sleep in six patients with pantothenate kinase-associated neurodegeneration.

Sleep Med 2021 08 27;84:389-396. Epub 2021 Jun 27.

Parkinson's Disease and Movement Disorders Unit, Neurology Department, Hospital Clínic de Barcelona, Barcelona, Catalonia, Spain; Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII), Barcelona, Catalonia, Spain; European Reference Network for Rare Neurological Diseases - Project ID No 739510, Spain. Electronic address:

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurologic disorder included in the group of neurodegeneration with brain iron accumulation diseases (NBIA). Information regarding sleep in patients with PKAN is limited.

Objectives: To describe the clinical and polysomnographic characteristics of sleep in six patients with genetically confirmed PKAN. Read More

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Changes in Cerebral Gray and White Matter in Patients with Pantothenate Kinase-Associated Neurodegeneration: A Long-Term Magnetic Resonance Imaging Follow-Up Study.

J Mov Disord 2021 May 26;14(2):148-152. Epub 2021 May 26.

Department of Radiology, CEDIMAT, Santo Domingo, Dominican Republic.

Objective: To determine the volume changes in gray and white matter during a long-term follow-up in patients suffering from pantothenate kinase-associated neurodegeneration (PKAN).

Methods: Magnetic resonance imaging was repeated in 13 patients and 14 age-matched controls after a mean interval of more than 7 years. T1-weighted sequences were evaluated by fully automated atlas-based volumetry, compared between groups and correlated with disease progression. Read More

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Eye of the Tiger Sign in Pantothenate Kinase-Associated Neurodegeneration.

Case Rep Radiol 2021 7;2021:6633217. Epub 2021 May 7.

Children's Hospital, Radiology Department, Mohamed V University, Rabat, Morocco.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation caused by a recessive mutation in pantothenate kinase 2 gene (PANK2). We present a case of an 11 year-old boy presenting extrapyramidal signs and developmental regression. T2-weighted images showed the classic eye of the tiger sign seen in pantothenate kinase-associated neurodegeneration. Read More

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Turnover rate of coenzyme A in mouse brain and liver.

PLoS One 2021 21;16(5):e0251981. Epub 2021 May 21.

ADME/DMPK Department, IRBM SpA, Pomezia, Roma, Italy.

Coenzyme A (CoA) is a fundamental cofactor involved in a number of important biochemical reactions in the cell. Altered CoA metabolism results in severe conditions such as pantothenate kinase-associated neurodegeneration (PKAN) in which a reduction of the activity of pantothenate kinase isoform 2 (PANK2) present in CoA biosynthesis in the brain consequently lowers the level of CoA in this organ. In order to develop a new drug aimed at restoring the sufficient amount of CoA in the brain of PKAN patients, we looked at its turnover. Read More

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October 2021

Rational Design of Novel Therapies for Pantothenate Kinase-Associated Neurodegeneration.

Mov Disord 2021 09 18;36(9):2005-2016. Epub 2021 May 18.

Departments of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.

Background: This review highlights the recent scientific advances that have enabled rational design of novel clinical trials for pantothenate kinase-associated neurodegeneration (PKAN), a rare autosomal recessive neurogenetic disorder associated with progressive neurodegenerative changes and functional impairment. PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in pantothenate kinase 2 (PANK2) enzyme activity, with consequent disruption of coenzyme A (CoA) synthesis, and subsequent accumulation of brain iron. The clinical phenotype is varied and may include dystonia, rigidity, bradykinesia, postural instability, spasticity, loss of ambulation and ability to communicate, feeding difficulties, psychiatric issues, and cognitive and visual impairment. Read More

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September 2021

Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives.

Orphanet J Rare Dis 2021 05 5;16(1):201. Epub 2021 May 5.

Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas, Universidad Pablo de Olavide, Carretera de Utrera Km 1, 41013, Sevilla, Spain.

Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological 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 the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Read More

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Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders.

Front Neurol 2021 15;12:629414. Epub 2021 Apr 15.

Department of Neurology With Friedrich Baur Institute, University Hospital of Ludwig-Maximilians-Universität München, Munich, Germany.

Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogeneous group of progressive neurodegenerative diseases characterized by iron deposition in the globus pallidus and the substantia nigra. As of today, 15 distinct monogenetic disease entities have been identified. 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). Read More

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