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Fatal Familial Insomnia
The First Account in a Family of Chinese Descent
Sian D. Spacey, MD;
Manuela Pastore, PhD;
Barbara McGillivray, MD;
Jonathan Fleming, MD;
Pierluigi Gambetti, MD;
Howard Feldman, MD
Arch Neurol. 2004;61:122-125.
Background Fatal familial insomnia (FFI) is an autosomal dominant disease linked to a mutation in the prion protein gene. Fatal familial insomnia is characterized by sleep disturbance and loss of neurons, with gliosis in the thalamic nuclei.
Objective To describe the clinical, neurophysiological, radiological, and neuropathological data in a Chinese family with FFI.
Setting Tertiary referral university hospital setting.
Patients Patient 1 was a 36-year-old man who presented with insomnia and myoclonus. In the subsequent 9 months, he developed ataxia and dementia, followed by death. Patient 2 was the aunt of patient 1, and presented at the age of 47 years with insomnia, myoclonus, and dementia; her condition declined during a 12-month period. Genetic analysis was performed, followed by neuropathological and biochemical analysis of the disease-associated form of the prion protein PrPSc on the postmortem brain specimen.
Results Molecular analysis demonstrated an aspartic acid to asparagine mutation at codon 178 and homozygosity for methionine at codon 129. Both patients showed severe neuronal loss and prominent gliosis in the thalamus and brainstem involvement, with evidence of astrogliosis in the inferior olivary nucleus. Patient 1 also had neuronal loss and astrogliosis in the region of the superior colliculus and in the periaqueductal region. PrPSc was detected on Western blot analysis, and had a wide distribution. The strongest signals were present in the amygdala, hypothalamus, caudate, parahippocampal gyrus, periaqueductal gray matter, and mediodorsal thalamus.
Conclusions To our knowledge, this is the first report of FFI in a family of Chinese descent. This supports the worldwide distribution of FFI, and despite differences in genetic background, the clinical and pathological findings are similar to those found in white patients with FFI.
From the Division of Neurology, the Department of Medicine (Drs Spacey and Feldman), and the Department of Psychiatry (Dr Fleming), The University of British Columbia, Vancouver; National Prion Disease Pathology Surveillance Center, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio (Drs Pastore and Gambetti); and the Department of Medical Genetics, B. C. Children's Hospital, Vancouver (Dr McGillivray).
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