A case of fatal familial insomnia in Africa.

Sir, Fatal familial insomnia (FFI) is an autosomal dominant prion disease linked to the D178N/129M haplotype in the prion protein gene, PRNP, and is the third in frequency among the genetic transmissible spongiform encephalopathies (TSEs) [4]. FFI is characterized by sleep and behavioral disturbances, autonomic alterations, ataxia, pyramidal signs, myoclonus, and late development of mental deterioration. FFI has been reported in families from Italy, Germany, Austria, Spain, the UK, France, Finland, the United States, Australia, Japan, and China [4, 7]. Here we describe the occurrence of the disease in the African Continent. A 45-year-old man, born in Morocco (Greater Casablanca region), was admitted after a five-month history of diplopia, and worsening unsteady gait. When specifically asked he reported a nine-month history of insomnia with total sleep time decreasing from 7 to 5 h per night. In addition he had developed excessive sweating, erectile dysfunction, and a ‘‘gasping’’ breathing. He reported that a similar disease was present in several members of in his family (Fig. 1, genealogical tree) who died after about one year of a progressive neurological illness. He had directly observed the evolution of the disease of his mother and three uncles (III-3, III-1, III-2, III-7 in the figure) which was characterized by disequilibrium, diplopia, speech disorder, insomnia, and late cognitive deterioration. He also gave us clinical records of a cousin (IV-9 in the figure) who had suffered from the ‘‘disease of the family’’. Neurological examination at admission showed horizontal and vertical saccades of the eyes in primary position with horizontal and vertical diplopia. The finger-to-nose test showed mild dysmetria with irregular tremor. Spontaneous and evoked myoclonus was evident, either segmental or massive, at the extremities and at the trunk; tendon reflexes were brisk. Gait was severely ataxic with retropulsion and with a trunk-extremity dissinergy. Neuropsycological examination showed only a mild deficit in long-term verbal memory. EEG showed no periodic discharges. In the CSF the 14-3-3 protein was absent and total tau protein was 120 pg/ml (normal values:141 ± 107 pg/ml). Four consecutive 24-h polysomnographic recordings (PSG) revealed marked reduction of total sleep time (range: 229–340 min; NV: 440 min) and total nocturnal sleep time (range: 123–290 min; NV: 420 min). Sleep efficiency ranged between 26 and 60% (NV [ 85%). Sleep was fragmented by frequent and sometimes prolonged periods of wakefulness. All sleep phases were represented but typical sleep figures (K-complexes and sleep spindles) were markedly reduced. REM sleep was characterized by physiological muscle sleep atonia; both during the night and during daytime naps REM sleep latency was abnormally short. These features were consistent with previous reports on FFI [5]. Brain MRI with diffusion weighted imaging and with spectroscopy, was reported as normal. Analyses of DNA from peripheral leukocytes, revealed the D178N mutation and methionine/valine heterozygosity at the polymorphic 129 codon of the PRNP gene. The mutated allele had methionine at codon 129 and an R3-R4 24 bp deletion. E. Baldin S. Capellari F. Provini P. Corrado R. Liguori P. Parchi P. Montagna P. Cortelli (&) Department of Neurological Science, University of Bologna, via Ugo Foscolo, 7, Bologna, Italy e-mail: pietro.cortelli@unibo.it