Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family

Objective: To describe an unusual kindred with adult-onset ataxia and thala mic lesions detected by brain MRI. Methods: The authors characterized clini cal, laboratory, and pathologic features of the disease and sought linkage to previously recognized ataxia loci. Results: Two sisters and a brother de veloped progressive ataxia, dysarthria, mild cognitive impairment, and sens orimotor neuropathy at age 30, combined with epilepsy in one sibling. MRI s howed symmetric thalamic lesions, changes in brainstem gray matter, and whi te matter changes in the cerebellum. Autopsy in one of the patients reveale d neuronal degeneration with a peculiar vacuolar change in thalamus, probab ly representing transsynaptic degeneration in response to deafferentation. Neuronal and secondary tract degeneration was observed in the spinal cord, cerebellum, and brainstem suggesting a spinocerebellar degeneration. The di sorder appears to be transmitted as an autosomal recessive trait. Genetic a nd sequence analysis of the FRDA gene and comprehensive laboratory examinat ions excluded Friedreich's ataxia and other similar recessive diseases. Con clusion: Adult-onset recessive ataxia with bilateral thalamic lesions in th is family may represent a distinct hereditary spinocerebellar ataxia.