Fatal familial insomnia is an autosomal dominant neurodegenerative disorder characterised by insomnia, rapidly progressive dementia, dysautonomia, myoclonus and pyramidal signs. We report a 60 year old man who presented with an eight month history of progressive cognitive decline associated with dysautonomia, anaemia, hyponatraemia due to syndrome of inappropriate ADH secretion, hypersomnia with oneiric behaviours, intermittent diplopia, gait disturbance, myoclonus and well formed visual hallucinations. The anaemia was secondary to myelodysplasia from a 20q chromosome deletion. The patient’s prion protein genetic sequencing revealed a D178N mutation on chromosome 20p with codon 129 polymorphism that was homozygous for methionine, consistent with a diagnosis of fatal familial insomnia. This was confirmed on post-mortem examination of the brain which showed thalamic and inferior olivary nucleus atrophy with severe neuronal loss, gliosis and mild spongiosis, but lack of significant cortical spongiosis and negative prion protein (3F4 and PrP) immunohistochemistry staining. Hypothalamic changes were also present and may explain SIADH. The patient’s older sister also had rapidly progressive dementia with myoclonic jerks, hyponatraemia due to SIADH and anemia. There have been no previous cases described in the literature between the association of prion gene mutation on chromosome 20p, and 20q deletion leading to anaemia secondary to myelodysplasia. It is unclear if prion protein may have some role in the pathogenesis of anaemia which appears acquired.