ABSTRACT
BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is due to a CAG expansion (CAGexp) at ATXN2. SCA2 presents great clinical variability, alongside characteristic ataxia with saccadic slowness. AIMS: To study parkinsonism, dementia, dystonia, and amyotrophy as subphenotypes of SCA2, and to explore the effect of CAG repeats at different loci and of mitochondrial polymorphism A10398G as modifiers of phenotype. METHODS: Symptomatic subjects were classified by presence/absence of neurological signs mentioned above; SARA and NESSCA scores were obtained. CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7 and RAI1, and polymorphism A10398G at mtDNA were established. Group characteristics were compared, with a p < 0.05. RESULTS: Forty-eight SCA2 individuals were included. Age at onset, CAGexp, and disease duration explained 53% and 43% of SARA and NESSCA variations, respectively. CAGexp of subjects with and without parkinsonism were different (medians of 42 and 39 repeats) as well as of subjects with and without dystonia (44 and 40 repeats). Amyotrophy was not significantly related to any variable under study. Concerning polymorphism A10398G, 83% of subjects with and 34% of those without cognitive decline carried 10398G at (p = 0.003). DISCUSSION: Treating the four phenotypic subgroups as outcomes was a valid strategy to identify modifiers of disease. Among correlations found, some confirmed previous reports, such as that between dystonia and CAGexp. Of note was the association between cognitive decline and the variant G at mitochondrial polymorphism A10398G, a variant formerly related to earlier ages at onset in SCA2.
Subject(s)
Ataxin-2/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/physiopathology , Adult , Aged , Alanine/genetics , Dementia/genetics , Dementia/physiopathology , Dystonia/genetics , Dystonia/physiopathology , Female , Glycine/genetics , Humans , Male , Middle Aged , Parkinsonian Disorders/genetics , Parkinsonian Disorders/physiopathology , Phenotype , Risk Factors , Young AdultABSTRACT
X-linked adrenoleukodystrophy heterozygote women can present adult onset myeloneuropathy and little is known about its natural history. We aimed to describe the progression rate of the neurological impairment in the prospective follow-up of our cohort and to look for prognostic factors. The neurological scales Japanese Orthopaedic Association (JOA) and Severity Score System for Progressive Myelopathy (SSPROM) were applied at baseline in 29 symptomatic carriers and in follow-up visits. Age at onset, disease duration, X inactivation pattern, determination of the allele expressed, plasma levels of the very long chain fatty acids and of the neuron-specific enolase, and somato-sensory evoked potentials, were taken at baseline. The slope of the linear regression of both JOA and SSPROM versus disease duration since the first symptom was estimated using mixed modeling. JOA and SSPROM decreased 0.42 and 1.87 points per year, respectively (p < 0.001). None of the parameters under study influenced these rates. We estimated that the number of carriers per arm needed in a future 12 month trial with 80% power and a 50% reduction in disease progression would be 225 women for JOA and 750 for SSPROM. The progression rates of the studied neurological scales were small, did not depend on any modifier factor known, and reflected the characteristically slow worsening of symptoms in X-ALD heterozygotes. Better biomarkers are still necessary for future studies.
Subject(s)
Adrenoleukodystrophy/diagnosis , Adrenoleukodystrophy/genetics , Disease Progression , Heterozygote , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/genetics , Adult , Cohort Studies , Female , Follow-Up Studies , Humans , Middle Aged , Prospective Studies , Young AdultABSTRACT
O envelhecimento populacional brasileiro acarretou a necessidade de propostas de políticas públicas voltadas para o novo cenário demográfico. Um grande desafio para técnicos da área da saúde é a criação de um centro de referência secundária capaz de responder às demandas geradas pelas doenças crônicas (hipertensão e diabetes), de grande prevalência em idosos e que resultam em alta morbimortalidade. Como parte integrante de uma rede assistencial, o centro de referência secundária proposto visa ao ferecer profissionais especializados, recursos tecnológicos para apoio diagnóstico e terapêutico, tendo como parceiro imprescindível a atenção primária à saúde. Este artigo apresenta uma proposta de centro de referência secundário em hipertensão e diabetes e uma carteira de serviços proposta e seu cenário de inserção em uma rede assistencial.
