RESUMO
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients. Therefore PKAN is also classified together with other rare neurodegenerative diseases like Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) into the Neuroacanthocytosis (NA) syndromes. It has not been investigated yet whether acanthocytosis in PKAN is associated with a specific subset of Pank2 mutations. In this study, we analyzed acanthocytosis of a cohort of 25 PKAN patients from the Dominican Republic that are homozygous for the c.680 A>G mutation in the PANK2 gene as compared to control donors that are heterozygous or wild-type with respect to this mutation. 3D modeling of this mutation indicated that the replacement of a tyrosine by a cysteine at position 227 in Pank2 disrupts a polar interaction within the A domain of the enzyme. Mean acanthocyte count was elevated in the cohort of patients, however, acanthocytosis varied among the patients with nearly half of them showing high (>20%) or elevated acanthocytosis and the rest showing mild (6-10%) or no (<6%) acanthocytosis. Heterozygous control donors revealed a tendency to mild acanthocytosis. Based on the insight that Pank2 is a normal constituent of red blood cells and de novo biosynthesis of coenzyme A is likely to take place in the erythrocyte cytosol we propose a hypothetical model that accounts for the variability in the occurrence of acanthocytic cells in PKAN.
Assuntos
Abetalipoproteinemia/diagnóstico , Acantócitos/patologia , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Polimorfismo de Nucleotídeo Único , Abetalipoproteinemia/genética , Abetalipoproteinemia/patologia , Adolescente , Adulto , Criança , Estudos de Coortes , República Dominicana , Estabilidade Enzimática , Homozigoto , Humanos , Modelos Moleculares , Neurodegeneração Associada a Pantotenato-Quinase/sangue , Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/química , Adulto JovemAssuntos
Acantócitos/patologia , Anemia Hemolítica/patologia , Sobrecarga de Ferro/sangue , Cirrose Hepática Alcoólica/sangue , Fígado/patologia , Pâncreas/patologia , Anemia Hemolítica/etiologia , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/patologia , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Baço/patologiaRESUMO
Chorea-acanthocytosis (ChAc) is a neurodegenerative disorder characterized by chorea, neuropsychiatric disturbances and acanthocytosis, caused by mutations of VPS13A. This gene produces the protein chorein which is absent in patients with ChAc on Western blot assay. We report the first two Brazilian patients with ChAc confirmed by chorein detection. Patient 1 is a 36-year-old man with chorea, epilepsy, myopathy, and suicidal ideation. Patient 2 is a 60-year-old woman with a 30 year history of psychiatric disturbances, epilepsy, choreic movements, and myopathy. Both patients had acanthocytosis, elevated creatine kinase (CK), and absence of chorein on Western blot analysis. The presence of chorea and neuropsychiatric disturbances associated with elevated CK levels, epilepsy, hyporeflexia, and acanthocytosis suggests the diagnosis of ChAc. Chorein assay of peripheral blood confirms the diagnosis.
Assuntos
Acantócitos/patologia , Coreia/complicações , Adulto , Brasil , Coreia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Proteínas de Transporte Vesicular/metabolismoRESUMO
We present a 45 years old man with neuroacanthocytosis. This gentleman has complex partial seizures and generalized tonic-clonic seizures, as well as movement disorders characterized by chorea and orofacial diskinesia. Complementary examination shows acanthocytosis of 11% on peripheral blood, irritative focus on right temporal lobe on EEG, serum creatinokinase of 101 U/l and volume reduction and hypersignal on caudate nucleus and putamen bilaterally on MRI.
Assuntos
Acantócitos/patologia , Coreia/diagnóstico , Coreia/tratamento farmacológico , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/tratamento farmacológicoRESUMO
Relatamos o caso de um paciente de 45 anos com neuroacantocitose. O paciente apresenta crises parciais complexas como automatismos e crises generalizadas tônico-clônicas, assim com distúrbios do movimento caracterizados por coréia do tronco e membros superiores, e discinesia orofacial. Os exames complementares revelam acantocitose de 11 por cento, eletrencefalograma com foco irritativo no lobo temporal direito, creatino fosfoquinase sérica de 101 U/L e imagem de ressonância magnética com redução volumétrica e hiper-intensidade do sinal no núcleo caudado e putâmen bilateralmente.