Our unfortunate patient had familial prion disease which results in the destruction of the thalamus and corpus striatum. There is no cure for this condition and it is uniformly fatal.
The gene for prion protein (PRPc) isfound in all mammals and appears on chromosome 20. It can spontaneously mutate as in our patient or a malformed protein can be acquired by eating infected protein. When prion proteins are malformed (PRPsc) they act like viruses and cause other prion proteins( or alpha-synuclin) to be misfolded as well. This makes them unique since all other infectious agents contain nucleic acids ( DNA or RNA) .
Prions were initially identified as the causative agent in acquired prion diseases in animals such as scrappie in sheep and bovine spongiform encephalopathy ( mad cow disease). In humans it causes Creutzfeldt-Jakob disease , fatal familial insominia and kuru. After crossing the blood brain barrier, the abnormal prion proteins are reproduced in the endoplasmic reticulum of the cell and cause misfolding of other normal prion proteins. They then migrate to the surface of cells where they form amyloid plaques which disrupt structure and cause “holes” in the tissue because of vacuoles in the neurons.
The acquired form of prion disease kuru( which means to shake) was frequent in New Guinea where the Fore people historically ate the brains of dead relatives. When the Fore people stopped eating human meat about 50 years ago, the disease lingered due to its long incubation period. The last known kuru victim died in 2009. Interestingly, in studying the epidemic, some people were found to be immune, suggesting that a long period of cannibalism had allowed the development of resistance.
The incubation period for prion disease is 5-20 years but once symptoms occur it rapidly leads to brain damage and death.. The striatum coordinates cognition including decision making, motivation and action planning. The loss of these parts of the brain results in dementia, ataxia, memory loss and seizures. Our patient was counselled as to her prognosis .
The disease affects one in a million people. Although rare, it is thought that alzheimer’s may also act in a prion like fashion which makes a cure for prion disease the “holy grail” of neurodegenerative research.
Alberti S, Halfmann R, King O, Kapila A, Lindquist S A systematic survey identifies prions and illuminates sequence features of prionogenic proteins Cell 2009. 137(1) 146-58.
Prusiner SB Molecular biology of prion diseases Science. 1991 252 1515-1522.
Alpers, M. A history of kuru. 2007 Papua and New Guinea Medical Journal 50 (1-2) 10-1p