Multiple system atrophy (Multiple system atrophy) - Gen SNCA and COQ2
Multiple system atrophy, also known as Shy-Drager syndrome, progressive brain disorder that affects movement and balance and in which the autonomic nervous system is altered. They described two main types of multiple system atrophy, which are distinguished by their principal signs and symptoms at the time of diagnosis. In one type, known as MSA-P, they are a group of predominant motion abnormalities parkinsonism type. These abnormalities include bradykinesia, muscular rigidity, tremor and postural instability. The other system atrophy, known as MSA-C, characterized by cerebellar ataxia, causing problems with coordination and balance. This form of the disease may also include dysarthria and control problems of eye movement. Both forms of multiple system atrophy associated with abnormalities of the autonomic nervous system. The most common symptoms include orthostatic hypotension, urinary difficulties and erectile dysfunction in men.
In general, multiple system atrophy occurs in older adults. On average, signs and symptoms appear about 55 years. These signs and symptoms become worse over time and affected individuals survive an average of 10 years after diagnosis.
This disease is a complex disorder that is likely due to the interaction of multiple genetic and environmental factors. Some of these factors have been identified, but many remain unknown. They have examined environmental factors that might contribute to disease risk. It is likely that exposure to solvents, certain types of plastics or metals, and other toxins could be potential associated with the disease. However, it has not confirmed these associations. The confirmed genetic risk factors consist of the SNCA gene variants and the COQ2 gene.
The SNCA (synuclein alpha) gene on the long arm of chromosome 4 (4q21), encodes a protein called alpha-synuclein is abundant in normal brain cells and, in smaller amounts, in the heart, muscles and other tissues. In the brain, alpha-synuclein is mainly found in presynaptic terminals of neurons. Within these structures, the alpha-synuclein interacts with lipids and proteins. Presynaptic terminals release neurotransmitters from synaptic vesicles, which transmit signals between neurons and are essential for normal brain function. Although the function of alpha-synuclein is unclear, it is likely to play an important role in maintaining synaptic vesicles in the presynaptic terminals. In addition, it can help regulate the release of dopamine, a type of neurotransmitter that is critical to control the start and stop of voluntary and involuntary movements.
They have been identified variations in the SNCA gene that increase the risk of multiple system atrophy. These variations change a single nucleotide in the SNCA gene. Work is being done to determine whether these changes alter the function of the protein alpha-synuclein and how they influence the risk of developing the disease. Variations in the SNCA gene appear to affect the risk of disease in people of European descent; However, some studies suggest that changes in this gene are not associated with multiple system atrophy in Chinese or Korean population. It is unclear whether changes in the SNCA gene is a risk factor for this disease in people of other ethnic and geographic origins.
The COQ2 (coenzyme Q2, polyprenyltransferase) gene, located on the long arm of chromosome 4 (4q21.23), encoding the coenzyme Q2. This enzyme carries out a step in the production of coenzyme Q10, which has several critical functions in cells throughout the body. In mitochondria, coenzyme Q10 plays an essential role in the process of oxidative phosphorylation, which converts energy from food into a form that cells can use. Coenzyme Q10 is also involved in the production of pyrimidines, and certain RNA molecules such as ATP and GTP serving as an energy source in cells. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by free radicals.
Studies indicate that several variations in the gene COQ2 increase the risk of multiple system atrophy. Identified variations consist of amino acid changes in the coenzyme Q2. Most of the variations are very rare, but a genetic change which replaces the amino acid valine for alanine at amino acid position 393 (Val393Ala or V393A) is relatively frequent. Studies suggest that these variations, including V393A, are associated with an increased risk of developing multiple system atrophy in the Japanese population. However, studies have found a correlation between genetic variations and multiple system atrophy COQ2 in other locations, including Korean, Europeans and Americans. It remains unclear whether genetic variations COQ2 represent a major risk factor for this disease. However, it is believed that changes in the COQ2 gene could alter the activity of coenzyme Q2, which affect the production of coenzyme Q10. Coenzyme Q10 concentrations are reduced in the brains of people with multiple system atrophy. A reduction in the amount of coenzyme Q10 can alter oxidative phosphorylation and increase the vulnerability of cells to damage from free radicals. However, it is not known how these changes are related to the characteristics of this disease.
Most cases are sporadic multiple system atrophy, which means that occur in people with no history of disease in your family. Rarely inherited cases have been identified although in these cases, the pattern of inheritance of the disease is unclear.
Tests in IVAMI: in IVAMI perform detection of mutations associated with multiple system atrophy, by complete PCR amplification of the exons of SNCA and COQ2 genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).