RESUMO
Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 µg/L), AOA2 (15-65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.
Assuntos
Apraxias/congênito , Ataxia Telangiectasia/sangue , Ataxia Telangiectasia/diagnóstico por imagem , Síndrome de Cogan/sangue , Síndrome de Cogan/diagnóstico por imagem , Imagem Multimodal , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Apraxias/sangue , Apraxias/diagnóstico por imagem , Apraxias/genética , Ataxia Telangiectasia/genética , Criança , Pré-Escolar , Síndrome de Cogan/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , alfa-Fetoproteínas/genéticaAssuntos
Encéfalo/patologia , Transtornos da Consciência/etiologia , Hipoglicemia/diagnóstico , Imageamento por Ressonância Magnética , Quadriplegia/etiologia , Idoso de 80 Anos ou mais , Apraxias/sangue , Apraxias/etiologia , Transtornos da Consciência/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diagnóstico Diferencial , Erros de Diagnóstico , Disartria/sangue , Disartria/etiologia , Feminino , Humanos , Hipoglicemia/complicações , Imageamento Tridimensional , Insulina/uso terapêutico , Quadriplegia/sangue , Acidente Vascular Cerebral/diagnósticoRESUMO
Ataxia with oculomotor apraxia type 2 (AOA2), a neurodegenerative disorder with juvenile to adolescent onset is caused by mutations within the SENATAXIN gene ( SETX). We performed molecular analyses in six patients showing clinically an AOA2 phenotype and moderate to significant elevated serum alpha-fetoprotein levels. Sequencing the 24 coding exons and flanking intronic sequences revealed 11 novel DNA variations, including seven unknown missense mutations, a dinucleotide deletion, a four-nucleotide deletion affecting the 5' splice site of exon 22 and two sequence variations, which are considered to be polymorphisms. By molecular testing the clinical diagnosis has been confirmed in all patients.
Assuntos
Apraxias/genética , Ataxia Cerebelar/genética , Análise Mutacional de DNA , Doenças do Nervo Oculomotor/genética , RNA Helicases/genética , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Alelos , Apraxias/sangue , Apraxias/diagnóstico , Atrofia , Ataxia Cerebelar/sangue , Ataxia Cerebelar/diagnóstico , Cerebelo/patologia , Deleção Cromossômica , Consanguinidade , DNA Helicases , Éxons/genética , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Enzimas Multifuncionais , Mutação de Sentido Incorreto , Exame Neurológico , Doenças do Nervo Oculomotor/sangue , Fenótipo , Polimorfismo Genético/genética , Adulto JovemRESUMO
A 57-year-old man on long-term renal dialysis presented with speech dyspraxia, a symptom characteristic of early aluminium encephalopathy. Once fully developed, this condition has a poor prognosis despite deferoxamine (DFO) treatment.