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Pathology => Human Diseases => Creutzfeldt-Jakob Disease
Creutzfeldt-Jakob Disease
INTRODUCTION
Creutzfeldt-Jakob Disease, form of human spongiform encephalopathy caused by an infection of the brain, probably by a particle called a prion. The disease causes fatal degradation of brain tissue and produces a dementia that affects men and women, often between the ages of 50 and 65. Some 90 percent of cases progress to death within one year, sometimes within one month-symptoms include loss of speech, difficult swallowing, rigid limbs, and contraction of the facial muscles, with death often resulting from a complication following these symptoms. The remaining 10 percent of cases develop dementia and may slowly decline over several years. There is no record of anyone recovering from the disease and there is no known treatment.
Creutzfeldt-Jakob disease is found worldwide but is relatively rare, affecting about 0.9 people per million in the United States. The mean age of death is 67 years. Deaths from Creutzfeldt-Jakob disease are uncommon in people under age 50. In people age 70 to 74 years, the disease causes 5.9 deaths per million people.
CAUSES
Creutzfeldt-Jakob disease is associated with prions, mutated forms of a normal protein produced in nerve cells, white blood cells, muscle cells, and the cells of many other tissues. Just how prions cause the disease symptoms remains unclear. There are three types of the disease: sporadic, genetic, and iatrogenic.
Sporadic Creutzfeldt-Jakob disease is the most common form and accounts for around 85 percent of all human prion disease. In such cases, the gene coding for the prion protein undergoes a spontaneous mutation. The gene then codes for the abnormal, infective form of the protein. A small number of mutant cells producing a small amount of prion protein can initiate a progressive infection. Recent research suggests that this occurs because the abnormal protein can transform normal molecules by causing them to change their configuration.
Genetic Creutzfeldt-Jakob disease causes 10 to 15 percent of prion disease cases. It occurs when a mutant prion gene is passed genetically from one generation to another. In families expressing the mutant gene, about half the members die of the disease.
Iatrogenic Creutzfeldt-Jakob disease results from an individual with the disease infecting a healthy individual. This is rare but known cases involve surgery or transfusion procedures such as corneal transplants or human growth hormone injection. The disease has been characterized only recently and it may take up to 20 years to express itself or may not be recognized until the patient dies. For these reasons, many individuals may have been infected inadvertently with Creutzfeldt-Jakob disease in the past and could be at risk of developing the disease. It is estimated that 25,000 such cases exist worldwide.
Creutzfeldt-Jakob disease is similar to bovine spongiform encephalopathy (BSE), a prion-related brain disease of cows discovered in the United Kingdom in 1986 and commonly known as mad cow disease. Mad cow disease can be transmitted from sheep to cows, but until recently there has been no significant evidence that beef contaminated with BSE can infect humans. Prions are generally species-specific-that is, they tend to affect species closely related to the organism originally producing the protein. For this reason, scientists thought it unlikely that humans could contract the disease from eating infected beef.
Nevertheless, in late March 1996 the British Ministry of Health announced the discovery of 10 cases of a newly described type of fatal CJD, called new variant CJD (nvCJD). The victims of nvCJD had distinct brain tissue abnormalities, they were all under the age of 42, and they had no hereditary record of the disease. Despite a lack of scientific evidence proving the cattle-human disease link, the British government admitted that the victims may have contracted the disease through contact with BSE-infected cattle. The announcement represented an about-face in the stance of the government, which had previously denied any possible link between BSE and human disease. Rising concern over the possibility of transmission of BSE to humans from infected beef resulted in the banning of exported beef from the United Kingdom in 1996.
Although the hypothesis of the cattle-to-human transmission remains unproven, it is supported by the results of a number of scientific studies, including two released in 1997. Laboratory mice injected with brain tissue from BSE-infected cows and another group injected with brain tissue from nvCJD-infected humans both developed the same symptoms of brain degeneration and the infection was ultimately fatal in both groups. In addition, researchers found the same prion strain in both groups of mice. In one of the studies, researchers injected a third group of mice with tissue from humans who had died of classical CJD; these mice developed no symptoms and survived the trial.
In early 1998 scientists found that prions are found not only in the brain tissue of infected humans but in other organs and the blood as well. The potential public health problems have focused the attention of the medical community on the various forms of CJD and other prion diseases.
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