Spinocerebellar ataxia (NORD)

Definitions & Key takeaways

Spinocerebellar ataxia or SCA is a progressive, genetic, and often fatal neurodegenerative disorder with multiple types, caused by SCA gene mutations. These mutations result in degenerative changes in the cerebellum and the spinal cord, which causes progressive problems with coordination and balance, known as ataxia.

Symptoms of SCA vary depending on the subtype, but common ones include gait abnormalities, limb ataxia, dysarthria, nystagmus, and progressive difficulty with balance and coordination. Some subtypes of SCA can also cause vision problems, hearing loss, and cognitive impairment.

Diagnosis includes neuroimaging and genetic sequencing, and treatment options are mainly focused on managing symptoms and improving quality of life since there is no definitive cure. Physical therapy can help to maintain mobility and prevent falls, while speech therapy can help to improve communication abilities. In some cases, medications can be used to manage symptoms such as tremors or spasticity.

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Spinocerebellar ataxia or SCA refers to a group of rare genetically inherited conditions, caused by mutations in several types of SCA genes.
These mutations result in degenerative changes in the cerebellum and often, the spinal cord, which causes progressive problems with coordination and balance, known as ataxia.The cerebellum sits at the back of the skull, posterior to the brainstem.
Neurons send their axons carrying input from the spinal cord, the brain and the internal ear through the brainstem into the cerebellum.
Once there, the cerebellum uses this information to coordinate and plan movement as well as maintain balance.So, with mutations in the SCA genes, the cerebellum, along with the spinal cord, slowly degenerate.
In fact, many different gene mutations have been identified, each of which is known to cause different types of spinocerebellar ataxia.
The types are described using "SCA" followed by a number, according to their order of identification, so there’s SCA1 through SCA48, with SCA3 being the most common type.
However, in about 40% to 25% of the cases, the causative genes are still unknown. Now, most of these gene mutations are inherited in an autosomal dominant pattern, meaning that one copy of an altered SCA gene is enough to cause the disease.
Affected individuals have a 50% chance of passing on the altered gene to their child, causing that child to have the disease.
In some cases, the involved gene contains a triplet repeat, where the nucleotides C, A, and G are repeated multiple times in a row.
And since CAG codes for the amino acid glutamine, the encoded protein will have multiple extra glutamines in a row. The specific way in which extra glutamines causes the disease’s symptoms isn’t fully understood, but the abnormal protein seems to aggregate within the neurons of the cerebellum and spinal cord, causing them to die.
The expanded CAG repeats also affect DNA replication itself. When copying the mutated gene, DNA polymerase can basically lose track of which CAG it’s on and accidently add extra CAGs.
This expansion of the originally inherited gene means a child of a parent with the disease can inherit even more CAG repeats than the parent.
The higher the number of repeats in the protein, the earlier the age of onset and the more severe the symptoms.Symptoms vary depending on the type of spinocerebellar ataxia, but usually include poor coordination of hands, speech, walking and eye movements.
These symptoms may develop anytime from childhood to late adulthood.Diagnosis is based on a neurological examination and family history.
Neuroimaging tests like CT or MRI usually show cerebellar atrophy. Finally, genetic analysis of the involved genes confirms the diagnosis and helps identify the specific type of SCA.
Treatment involves physical therapy to strengthen the muscles, speech therapy, and special devices that assist in mobility like canes, braces and wheelchairs.
Other devices can also be used to assist with writing, feeding, and self-care. Even though there is no cure yet, research is going strong, and several medications that target different steps in the pathology of SCA have shown promise in animal models of the disease and have progressed to clinical trials in humans.##Summary Alright, as a quick recap, spinocerebellar ataxia is a group of progressive neurodegenerative diseases of genetic origin.
Many different types have been identified, most of which are autosomal dominant. It can present at any age with progressive loss of coordination of hands, speech, walking, and eye movements.
Diagnosis includes neuroimaging and genetic sequencing,