Background: Fatal Familial Insomnia (FFI) is an autosomal dominant multisystem prion disease, with sleep disorders often being the first presentation. Although autonomic dysfunctions are key features, the frequency and timing vary between reports, and may accompany early insomnia. Moreover, endocrine changes are reported, but diabetes rarely is - with unclear timing of onset in relation to the insomnia. Methods: N/A Results: Here we present a 46-year-old previously healthy male, who within 22 months prior to the onset of sleep disturbances, developed hypertension and diabetes. Then within 3-4 months after onset of sleep disturbances development tachycardia and diaphoresis. His sleep continued to deteriorate, and later developed bulbar impairment, ataxia, diplopia, sleep apnea and cognitive decline. He passed away 20 months from onset of insomnia. Polysomnography showed status dissociates and central apnea. He had positive genetic testing, PRNP c.532G>A (p.Asp178Asn) and PRNP c.385A>G (pMet129Val), a pathological confirmation, and a positive family history Conclusions: Here diabetes and hypertension significantly preceded sleep disturbances, and tachycardia and diaphoresis developed shortly after. This illustrates that dysautonomia and endocrine dysfunction may be unrecognized prodromes in some cases of FFI, and could be an early marker of clinical disease onset and therapeutic interventions, especially in genetically confirmed asymptotic patients.