1. Brain amino acid reductions in one family with chromosome 6p-linked dominantly inherited olivopontocerebellar atrophy
- Author
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Kish, Stephen J., Robitaille, Yves, El-Awar, Munir, Gilbert, Joseph, Deck, John, Chang, Li-Jan, and Schut, Lawrence
- Subjects
Brain diseases ,Genetic disorders -- Physiological aspects ,Olivopontocerebellar atrophies -- Physiological aspects ,Excitatory amino acids -- Abnormalities ,Olivopontocerebellar atrophies -- Genetic aspects ,Neurotransmitters -- Abnormalities ,Health - Abstract
Olivopontocerebellar atrophies are a group of disorders in which there is degeneration of the cerebellum, the underlying pons, and the olivary nuclei deep within the cerebellum. In about one third of cases, there is evidence of a genetic basis; most such cases are inherited as a dominant genetic trait. Families have been identified in which the gene responsible for this degeneration lies on the short arm of chromosome 6 (chromosome 6p). However, the exact cause of the degeneration remains unclear. One possibility is that abnormalities in neurotransmitter substances might contribute to the degeneration of brain cells within the affected regions. To examine this possibility, brains obtained at autopsy from six patients afflicted with chromosome 6p-linked dominantly inherited olivopontocerebellar atrophy were chemically analyzed. The amino acids aspartate and glutamate, both of which serve as neurotransmitter substances for some neurons, were reduced by 70 and 40 percent, respectively, in the cortex of the cerebellum in the affected brains. While some reductions would be expected in virtually any substance measured because of the reduction in the number of cells in the atrophied tissues, these reductions are larger than can be accounted for in this way. Aspartate and glutamate, as well as the related substance gamma aminobutyric acid, were also reduced in many other brain regions outside of the obviously affected areas. These reductions, which ranged from 10 to 30 percent, suggest that the metabolic abnormality responsible for the degeneration is not necessarily limited to the most obviously affected areas. In contrast, other important neurochemical substances, including taurine, glutamine, and ortho-phosphoethanolamine, appear not to be directly involved in the disease process and were found to be normal in all brain regions examined. The data from these six patients, all of whom were from the same affected family, indicate that a reduction in amino acid metabolism may be responsible for at least some cases of dominantly inherited olivopontocerebellar atrophy. Furthermore, the observed atrophy may be merely the most prominent symptom of a general defect affecting the rest of the brain as well. (Consumer Summary produced by Reliance Medical Information, Inc.)
- Published
- 1991