RESUMO
Late-onset spinal muscular atrophy associated with the VAPB gene is a slowly progressing, adult-onset, lower motor neuron disease with an autosomal dominant inheritance pattern. We present a male with progressive weakness beginning at age 44, predominantly in the proximal legs, fasciculations, and gait disturbance, with similar clinical syndrome in his mother. On physical examination, he presented weakness in 4 extremities, predominantly proximal, with atrophy and areflexia. The genetic study identified the c.166C > T mutation in the VAPB gene. The P56S mutation of the VAPB gene is associated with adult-onset spinal muscular atrophy and amyotrophic lateral sclerosis; It has been reported in different countries, although the prevalence is higher in Brazil, related to Portuguese migration. Clinically, the patients present with late-onset ALS or SMA. The disease usually onset in the fifth decade of life as progressive weakness, predominantly proximal in the lower extremities, without bulbar or respiratory involvement.
RESUMO
ABSTRACT Over the past 68 years, the Finkel type late-onset adult autosomal dominant spinal muscular atrophy (SMA) that is allelic with amyotrophic lateral sclerosis-8 (ALS8) gained a genotype-phenotype correlation among the motor neuron diseases through the work of groups led by Zatz and Marques Jr.
RESUMO Nos últimos 68 anos, a atrofia muscular espinhal (AME), autossômica dominante, de início tardio, em adultos, conhecida como doença de Finkel, que é alélica com esclerose lateral amiotrófica tipo 8 (ELA8), ganhou uma correlação fenotípica e genotípica dentre as doenças do neurônio motor, a partir da colaboração dos grupos de Zatz e Marques Jr.
Assuntos
Humanos , Atrofia Muscular Espinal/genética , Esclerose Lateral Amiotrófica/genética , Fenótipo , Proteínas de Transporte Vesicular/genética , MutaçãoRESUMO
Familial spinal muscular atrophy (FSMA) associated with the vesicle-associated membrane protein-associated protein B (VAPB) gene is a rare autosomal dominant disease with late onset and slow progression. We studied 10 of 42 patients from 5 families by taking clinical histories and performing physical exams, electrophysiological studies, and genetic tests. All patients presented late onset disease with slow progression characterized by fasciculations, proximal weakness, amyotrophy, and hypoactive deep tendon reflex, except two who exhibited brisk reflex. Two patients showed tongue fasciculations and respiratory insufficiency. Electrophysiological studies revealed patterns of lower motor neuron disease, and genetic testing identified a P56S mutation of the VAPB gene. Although it is a rare motor neuron disease, FSMA with this mutation might be much more prevalent in Brazil than expected, and many cases may be undiagnosed. Genetic exams should be performed whenever it is suspected in Brazil.
A atrofia espinhal progressiva familiar associada (AEPF) ao gene VAPB é uma doença autossômica dominante rara, de início tardio e lentamente progressiva. Estudamos 10 de 42 pacientes entre cinco famílias com AEPF, considerando a história clínica,o exame físico, a eletroneuromiografia e o teste genético. Todos os pacientes apresentaram inicio tardio, progressão lenta, fasciculações, fraqueza proximal, atrofia muscular e diminuição dos reflexos, exceto em um paciente em que os reflexos estavam vivos. Dois pacientes apresentavam fasciculações de língua e dois tinham fraqueza da musculatura respiratória. A eletroneuromiografia mostrou padrão de doença do segundo neurônio motor e o teste genético identificou a mutação P56S no gene VAPB. Embora seja uma doença rara, a AEPF associada a esta mutação pode ser mais prevalente no Brasil do que se acredita. Esta doença pode estar subdiagnosticada, devendo o teste genético ser realizado sempre que houver a suspeita diagnóstica.
