Autosomal dominant cerebellar ataxia

Autosomal Dominant Cerebellar Ataxia (ADCA) is a form of spinocerebellar ataxia inherited in an autosomal dominant manner. ADCA is divided into three types and further subdivided into subtypes know as SCAs (spinocerebellar ataxias).

Autosomal Dominant Hereditary Tree

Pathology: ADCA Subtypes

Type 1

Type 1 ADCA and is characterized by symptoms of ataxia as well as a number of other conditions depending on the subtype. Type 1 ADCA is divided into 3 subclasses based on pathogenesis of the subtypes each contain. Subtypes in the first subclass are caused by CAG nucleotide repeats in the DNA, which code for the amino acid glutamine. This glutamine is toxic to the cell on the level of proteins and has degenerative effects. Within the first subclass of type one are SCA1, SCA2, SCA3, SCA17, and DRPLA. This first subclass is the most common of Type 1 ADCAs with SCA3 being the most common subtype of all of type 1. The second subclass of Type 1 ADCA is also caused by the same nucleotide repeats but instead in RNA in a region that does not code proteins. Gene expression is affected instead of proteins in subclass two SCAs because of this. Subclass 2 contains SCA8, SCA10, and SCA12. The third and last subclass of ADCA type 1 is caused by mutation in genes and contains SCA13, SCA14, SCA15, SCA16, SCA27, and SCA28.

Type 2/3

Type II autosomal dominant cerebellar ataxia is made up by SCA7 and syndromes associated with pigmentary maculopathies. SCA7 is a disease that specifically displays retinal degeneration, along with the common degeneration of the cerebellar. Moving further into SCA7's pathology, a similar geneic process is described. The function of ATXN7 (an ataxin gene) is much like a component of the SAGA complex. The SAGA complex uses two histone-modifiying techniques to regulate transcription. These activities are the Gcn5 histone acetyltransferase and the Usp22 deubiquitinase. Mutant ATXN7 in HAT activity causes an increase in activity, which was reported from an in vivo analysis in the retina. There are also studies that show a loss in activity when human ATXN7 in yeast was used. The SCA7 autosomal-dominant inheritance pattern is similar to a mutant ATXN5-induced gain in Gcn5 HAT.

Symptoms and Diagnosis

Autosomal Dominant Cerebellar Ataxia primarily affects the cerebellum, as well as, the spinal cord. As discussed earlier, there are several kinds of ataxias which are grouped depending on how the specific disorder partners with cerebellar ataxia. Focusing on Ataxia type I, the most common disorder, which displays they symptoms of motor impairment, optic atrophy, oculomotor paralysis, and intelligence disorders. Symptoms of Autosomal dominant cerebellar ataxia typically are onset between the ages of twenty-five to forty-five years of age. In type I ataxia, equilibrium disorders indicate the presence of the disease. Speech production disorders are also another sign of cerebellum damage. This disorder is most frequently associated with the impairment of proprioception (perception of one's body parts in space). Later, paralysis of specific types of eye muscles, swallowing disorders, and impairment of the sphincter function can be associated to the primary condition. These various symptoms vary from different individuals and usually develop over a period of around 20 to 30 years.

Autosomal Dominant Cerebellar Ataxia is a genetically inherited condition that causes deterioration of the nervous system leading to disorder and a decrease or loss of function to regions of the body. Symptoms often begin during the patients twenties or thirties, although, childhood cases have been observed. Common symptoms include a loss of coordination which is often seen in walking, and slurred speech. Three main approaches of diagnosing the condition are the patients clinical history or their past health examinations, a current physical examination to check for any physical abnormalities, and a genetic screening of the patients genes and the genealogy of the family. The large category of cerebellar ataxia is caused by a deterioration of neurons in the cerebellum. Magnetic Resonance Imaging (MRI) is used to detect any structural abnormality such as lesions and tumors which are the primary cause of the ataxia. Computed tomography (CT) scans can also be used to view neuronal deterioration, but the MRI provides a more accurate and detailed picture. ADCA is a genetically inherited condition so a family screening and genealogy test are done to look for a pattern or lineage of the disease.</ref>

Treatments and Management

There is not a lot of information about treatments or therapies at this time. There are some ideas that give hope for future treatments. For the disease to manifest itself, these diseases require mutant protein expression. Manipulating the use of protein homoestasis regulators can be therapuetic agents. Also, a treatment to try and correct an altered function that makes up the pathology is one current idea. There is evidence that for SCA1 and two other polyQ disorders that the pathology can be reversed after the disease is underway. This was seen in Huntington's disease and spinalbulbar muscular atrophy.