Creutzfeldt–Jakob Disease

Creutzfeldt–Jakob disease (CJD, also known as Jakob–Creutzfeldt disease) is one of a group of rare fatal brain diseases caused by proteins called prions. The termprion is the name coined by Stanley Prusiner, for “proteinaceous infectious particles,” to describe the proteins he identified that cause transmissible spongiform encephalopathies (TSEs), or prion diseases. Prusiner was awarded the Nobel Prize for physiology and medicine in 1997 for his discovery of the prion.

The normal cellular form of prion protein (PrPC) is a protein found on cell membranes in humans and animals. The precise role of the prion protein in normal nerve cell function has yet to be determined. In prion disease, PrPC somehow manages to change shape from a primarily helical structure to a pleated sheet structure, becoming a misshapen prion protein called the prion or PrPSc. PrPSc becomes a template for conversion of existing normal prion proteins (PrPC) to PrPSc, beginning a devastating chain of reactions to convert nearby PrPC to become PrPSc. As many PrPC are converted to PrPSc, the accumulation of PrPSc injures nerve cell function, causing disease and ultimately leading to death. The altered function of nerve cells in the brain results in the broad spectrum of symptoms seen in patients with CJD.

CJD is characterized by a rapid deterioration in mental function, behavior, and movement. CJD affects roughly 1 person per 1 million people per year worldwide. In the United States, there are approximately 250 to 400 cases per year, with variation from year to year. There are three main types of CJD: sporadic (or classical), hereditary (genetic or familial), and acquired (transmitted through eating beef contaminated with prions or iatrogenic [occurring as the result of treatment by a health provider]). The following is a brief overview of each type of human prion disease.

Human prion diseases can be divided into three types by the way in which they occur: sporadic, genetic, and acquired. Sporadic orclassical Creutzfeldt–Jakob disease (sCJD) is the most common form of human prion disease, accounting for approximately 85% to 90% of cases. sCJD occurs without any known cause, without a family history of the disease, and in the absence of a mutation in the gene that codes for prion protein. The median age for onset of symptoms is roughly 68 years (average age of 60 years), with an average survival of roughly 8 months and approximately 90% of patients dying within 1 year from symptom onset. The most common first symptoms in CJD are cognitive such as confusion and memory loss. Other common first symptoms are dis-coordination, prominent behavioral and personality changes, and constitutional complaints (e.g., headache, malaise, fatigue).

Approximately 15% of human prion diseases aregenetic (heritable) and are due to a mutation (a change or an error) in the gene that codes for the prion protein. Genetic human prion diseases are generally classified into three types: familial CJD (fCJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), and the very rare fatal familial insomnia (FFI). Every person has two copies of every gene: one copy received from the mother and one copy received from the father. Human genetic traits are the result of having the two copies of each. A mutation is an error in a gene. For autosomal-dominant diseases, a person needs only one copy of a mutated gene to inherit the [Page 127]associated trait or disease; for recessive diseases (or traits), a person needs both copies of a gene to have mutations to get a disease or trait. Mutations in the prion protein gene are autosomal dominant. Thus, for a person with genetic CJD, with one normal and one mutated prion protein gene, each of the person's children has a 50% chance of receiving the bad copy. Thus, there is a 50% risk of transmitting the disease to each child regardless of the child's or parent's gender. Genetic forms of CJD often have a slower course and an earlier age of onset (typically in the 30s to 50s) compared with sCJD, with many patients living for several years after the onset of symptoms. More than 30 mutations in the prion protein gene have been identified. Patients with fCJD often present with symptoms and course similar to those for patients with sCJD. GSS usually begins with either parkinsonism (slowed movement) or ataxia (discoordination), and patients with FFI often develop intractable insomnia and/or dysautonomia; for example, problems maintaining blood pressure, body temperature, heart rate, or gut motility.

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