Spinocerebellar ataxia type 35

Spinocerebellar ataxia type 35 (SCA35) is a rare, inherited neurodegenerative disorder caused by mutations in the TGM6 gene, which encodes transglutaminase 6. This enzyme is predominantly expressed in the brain, particularly in the cerebellum, and plays a role in protein cross-linking. SCA35 primarily affects the central nervous system, with progressive cerebellar degeneration leading to worsening coordination and balance difficulties. It was first described in Chinese families but has since been identified in other populations. The hallmark features of SCA35 include progressive gait ataxia (unsteady walking), limb ataxia, dysarthria (slurred speech), and oculomotor abnormalities such as nystagmus and saccadic pursuit. Some patients may also experience upper motor neuron signs including hyperreflexia and spasticity, as well as tremor and cognitive difficulties. Brain imaging typically reveals cerebellar atrophy, which may be accompanied by mild cerebral cortical atrophy in some cases. The disease generally has an adult onset, with symptoms typically beginning between the third and fifth decades of life, though age of onset can vary. There is currently no cure or disease-modifying treatment for SCA35. Management is supportive and symptomatic, focusing on physical therapy and rehabilitation to maintain mobility and function, speech therapy for dysarthria, and occupational therapy to assist with daily activities. Medications may be used to manage specific symptoms such as tremor or spasticity. Genetic counseling is recommended for affected individuals and their families given the autosomal dominant inheritance pattern, meaning each child of an affected individual has a 50% chance of inheriting the causative mutation.

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