RESUMEN
INTRODUCTION: Family prion diseases are caused by mutations in the gene coding the prion protein (PrP), originating an altered isoform called prion. One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178. METHODS: We have studied two male patients, aged 43 and 49 years respectively, from the same family. RESULTS: The most significant symptoms were sleep disorders with agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was brief, the patient dying at a few months of the clinical debut. Sleep registries showed destructuration with total loss of the normal cycle of the phases and great decrease of the sleep spindles and K complexes in both cases. The polygraphy showed tachycardia and apnea pauses. In the molecular study, a mutation in the codon 178 was detected, both being methionine/methionine homozygotes at position 129. The most outstanding neuropathological abnormalities were located in the thalamus with gliosis and neuronal loss of anterior and dorsomedial ventral nuclei and also intense neuronal loss in olive of the first case. CONCLUSIONS: This study describes two new cases of FFI with genotype D178N-129M and short course classical phenotype. The polysomnography is essential in the diagnostic strategy of this disease whose neuropathological substrate is the thalamic alterations and of the inferior olive. Molecular biology permits an exact diagnosis of FFI although there is still controversy on the phenotypal variability and physiopathogenic mechanisms.
Asunto(s)
Insomnio Familiar Fatal , Adulto , Resultado Fatal , Genotipo , Humanos , Insomnio Familiar Fatal/patología , Insomnio Familiar Fatal/fisiopatología , Masculino , Persona de Mediana Edad , Fenotipo , PolisomnografíaRESUMEN
Introducción. Las enfermedades priónicas familiares son causadas por mutaciones en el gen que codifica la proteína priónica (PrP), originando una isoforma alterada denominada prión; una de las más infrecuentes es el insomnio letal familiar (ILF), entidad caracterizada por alteraciones en el sueño y que se asocia a una mutación en el codón 178. Métodos. Estudiamos dos pacientes varones de una misma familia de 43 y 49 años, respectivamente. Resultados. Los síntomas más relevantes fueron los trastornos del sueño con agitación, sueño fraccionado, ronquido e hipersomnia diurna; el curso evolutivo fue breve, falleciendo a los pocos meses del inicio clínico. En los registros de sueño se apreció en los dos casos desestructuración del mismo con pérdida total del ciclo normal de las fases y gran disminución de husos de sueño y complejos K. La poligrafía evidenció taquicardia y pausas de apnea. En el estudio molecular se detectó una mutación en el codón 178, siendo ambos homocigotos metionina/metionina en la posición 129. Las alteraciones neuropatológicas más llamativas se localizaron en el tálamo con gliosis y pérdida neuronal de núcleos ventral anterior y dorsomedial; además, intensa pérdida neuronal en la oliva bulbar del primer caso. Conclusiones. Este estudio describe dos nuevos casos de ILF con genotipo D178N-129M y fenotipo clásico de corta evolución. La polisomnografía es esencial en la estrategia diagnóstica de esta enfermedad, cuyo sustrato neuropatológico son las alteraciones talámicas y de la oliva inferior. La biología molecular permite un diagnóstico preciso del ILF, aunque sigue habiendo controversias sobre la variabilidad fenotípica y los mecanismos fisiopatogénicos (AU)
Introduction: Family prion diseases are caused by mutations in the gene coding the prion protein (PrP), originating an altered isoform called prion. One of the most uncommon is the fatal familial insomnia (FFI), an entity characterized by sleep disorders and that is associated to a mutation in codon 178. Methods: We have studied two male patients, aged 43 and 49 years respectively, from the same family. Results: The most significant symptoms were sleep disorders with agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was brief, the patient dying at a few months of the clinical debut. Sleep registries showed destructuration with total loss of the normal cycle of the phases and great decrease of the sleep spindles and K complexes in both cases. The polygraphy showed tachycardia and apnea pauses. In the molecular study, a mutation in the codon 178 was detected, both being methionine/methionine homozygotes at position 129. The most outstanding neuropathological abnormalities were located in the thalamus with gliosis and neuronal loss of anterior and dorsomedial ventral nuclei and also intense neuronal loss in olive of the first case. Conclusions: This study describes two new cases of FFI with genotype D178N-129M and short course classical phenotype. The polysomnography is essential in the diagnostic strategy of this disease whose neuropathological substrate is the thalamic alterations and of the inferior olive. Molecular biology permits an exact diagnosis of FFI although there is still controversy on the phenotypal variability and physiopathogenic mechanisms (AU)