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Creutzfeldt-Jakob disease (CJD) is one of a group of somewhat perplexing neurological diseases called the spongiform encephalopathies. This progressive dementing disease may occur sporadically or in family clusters. In all cases, however, the disorder may be experimentally or accidentally transmitted to some animals or people. The infectious agent is unlike any known bacteria or virus, and is referred to as a 'prion'. A gene has been found which codes for the prion protein (PrP). Mutations in this gene have been found in many, but not all, cases of CJD that have been examined. This failure to find a mutation in some cases does not necessarily mean there was no mutation, but that none of the already known mutations could be identified. It is possible to identify a new mutation by sequencing the gene, but this procedure can be quite laborious. Researchers have now used a technique that separates alleles to demonstrate that a mutation may be present. Most genes exist in two copies, one on the chromosome inherited maternally and the other on the paternal chromosome. For many genes, there may be a multitude of possibilities for these two locations; the individual possibilities are called alleles. Researchers have shown that a rapid laboratory technique is capable of indicating whether the two PrP genes in a CJD patient are the same or different; if the two are different, one is likely to contain some mutation. The technique works by 'melting' the DNA, using heat to separate the double-strands of the molecule. When the separate strands get back together, some of the pairs will consist of one normal and one mutant gene. These pairs will almost resemble a normal pair when separated. The slight difference between the perfectly matching (i.e. two normal or two mutant genes) and imperfectly matching (one normal and one mutant) pairs reveals the presence of a mutation. This technique was used to demonstrate the presence of a mutation in a patient with CJD disease who did not have any of the previously identified mutations. (Consumer Summary produced by Reliance Medical Information, Inc.)

There are a number of hereditary dystonias, disorders characterized by abnormalities in muscle tone. Progressive dystonia with diurnal variation (PDDV) is a specific dystonia which is inherited as an autosomal dominant trait, and in which the dystonia fluctuates throughout the day. Patients with PDDV are found to have decreased amounts of homovanillic acid in their cerebrospinal fluid (CSF), which suggests a deficiency in the synthesis of catecholamines. These patients are often helped significantly by the drugs levodopa and carbidopa, in a manner analogous to the treatment of Parkinson's disease. Another substance which is abnormally low in the CSF of patients with PDDV is biopterin. This substance serves as a necessary cofactor for a critical enzyme involved in the synthesis of dopamine and serotonin. For this reason, it was conjectured that the administration of tetrahydrobiopterin might benefit patients with PDDV. Four PDDV patients were treated with tetrahydrobiopterin, but an improvement was seen in only one. The patient who benefited from the treatment was not only the least severely affected, by was also the patient with by far the greatest amount of biopterin in her CSF to begin with. The authors conjecture that the disorder may involve the death of neurons, and that if too few responsive neurons are available, the tetrahydrobiopterin treatment cannot work. This conjecture would suggest that the responsive patient would be the one with the least neuronal damage, which is consistent with her laboratory values, which were closer to normal than those of the other patients. (Consumer Summary produced by Reliance Medical Information, Inc.)