Familial fatal insomnia: A Taiwanese case report

Abstract

Familial fatal insomnia (FFI) is a rare autosomal dominant inherited prion disease, which is characterized by severe sleep disorder, dysautonomia, motor signs and abnormal behavior. It is caused by D178N mutation in the prion protein gene accompanied by the presence of a methionine at the codon 129 polymorphic site on the mutated allele. Herein we reported a 37-year-old man presenting with unintentional weight loss of 24 kgs and progressive cognitive decline with episode of visual hallucination in 6 months. On examination, he had speech disturbance, general muscle wasting with muscle strength of 4/5, involuntary jerks, tremor-like movements, and gait disturbance. The electroencephalography did not show characteristic periodic sharp wave complexes and there was no focal brain lesion or abnormal cortical ribbon sign on magnetic resonance imaging of brain. Once he scored 11/30 on the Mini-Mental State Examination (MMSE) but he became speechless and unresponsive to verbal command in 1 month. He soon developed dysphagia and stridor during sleep. He was died of pneumonia. We didn't have chance to perform polysomnography although sleep disturbance was mentioned by his family. The CSF was acellular and normal biochemistry except positive for 14–3-3 protein. Genetic analysis by the Taiwan Centers for Disease Control identified D178N and M129 V mutations of PRNP gene. Early diagnosis of FFI might be challenging in such case because of low sensitivity of diagnostic tests and absence of family history. Rapidly progressive dementia with drastic weight loss can be an important clinical clue and genetic analysis is required for diagnosis.