RESUMO
BACKGROUND: The term chorea-acanthocytosis describes a heterogeneous group of neurodegenerative disorders with variable clinical features and modes of inheritance. The characteristic acanthocytic appearance of red blood cells is attributed to abnormalities of a membrane protein, band 3, although the relationship between this and the neurodegenerative process has yet to be determined. OBJECTIVE: To describe features of phenotype, inheritance, and neuropathological findings in a family with this disorder. METHODS: Clinical and hematologic evaluations were performed on all available family members and neuropathological examination was performed on one case. RESULTS: Autosomal dominant inheritance was evident, with variable clinical features of chorea or parkinsonism, marked cognitive changes, but no seizures or peripheral neurologic abnormalities. Abnormalities of band 3 were demonstrated on gel electrophoresis of red blood cell membranes. Neuropathological examination revealed severe neuronal loss of the caudate-putamen and intranuclear inclusion bodies in many areas of the cerebral cortex. These inclusion bodies were immunoreactive for ubiquitin, expanded polyglutamine repeats, and torsinA. CONCLUSIONS: This family extends the genetic spectrum of chorea-acanthocytosis to include autosomal dominant inheritance, possibly due to expanded trinucleotide repeats. Intraneuronal inclusion bodies have recently been associated with a wide range of inherited neurodegenerative disorders and may provide a clue to etiopathogenesis, in addition to potentially indicating a function of torsinA.
Assuntos
Coreia/genética , Coreia/patologia , Corpos de Inclusão/química , Corpos de Inclusão/patologia , Neurônios/patologia , Peptídeos/análise , Acantócitos/patologia , Adulto , Atrofia , Córtex Cerebral/química , Córtex Cerebral/patologia , Feminino , Humanos , Corpos de Inclusão/genética , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neurônios/química , LinhagemAssuntos
Responsabilidade pela Informação/legislação & jurisprudência , Aconselhamento Genético/legislação & jurisprudência , Doenças Genéticas Inatas/prevenção & controle , Papel do Médico , Polipose Adenomatosa do Colo/genética , Adulto , Criança , Confidencialidade/legislação & jurisprudência , Humanos , Masculino , Imperícia/legislação & jurisprudência , Fatores de RiscoRESUMO
Three patients from a previously described family with autosomal dominant chorea-acanthocytosis were found to have the CTG trinucleotide repeat expansion mutation of the junctophilin-3 gene associated with Huntington's disease-like 2 (HDL2). One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis.