Cerebellar Ataxia, Early-Onset, With Retained Tendon Reflexes

Clinical Features

During a comprehensive clinical and genetic study of families with progressive inherited spinocerebellar degeneration, Harding (1981) described a 'new ataxic syndrome,' occurring at a young age and clinically distinct from Friedreich ataxia (229300). The disorder was characterized by onset in the first or second decade, preservation of tendon reflexes, and a less severe course than in Friedreich ataxia. Harding (1981) labeled the disorder 'early-onset ataxia with retained tendon reflexes' (EOCA). Other cases were reported by Ozeren et al. (1989), Filla et al. (1990), and Klockgether et al. (1991).

Mielke et al. (1998) described a family with 2 members who had EOCA with retained tendon reflexes and, in addition to their motor deficits, had progressive impairment of cognitive and visuospatial abilities. They used positron emission tomography (PET) to analyze longitudinally regional cerebral glucose metabolism. By this method, they demonstrated reduced cerebellar benzodiazepine receptor binding which had not been shown in Friedreich ataxia or in olivopontocerebellar atrophy. The authors suggested that the finding may be useful for differentiation of EOCA from other types of cerebellar ataxia. In comparison to age-matched control subjects, these patients showed a global metabolic decline and predominant hypometabolism in the thalamus and cerebellum. The progressive metabolic derangement may be explained by a disturbed integrity of cognition-related networks resulting from secondary degeneration of cerebello-thalamo-cortical projections. One of the patients was a woman who noticed onset of ataxia at the age of 15 years and became wheelchair-bound over the next 4 years. A brother showed progressive impairment of movement abilities starting at the age of 21 years and became wheelchair-bound at the age of 22 years.

Inheritance

Chio et al. (1993) ascertained 40 cases diagnosed between 1940 and 1990 in a defined area of northwestern Italy. The ascertainment probability was 85.7%. The segregation analysis by the Weinberg proband method and 'singles' method under incomplete ascertainment was compatible with autosomal recessive inheritance. The point prevalence ratio was 1/100,000 population. The birth incidence rate was 1/48,000 live births. Gene frequency was estimated to be 1/218. The ratio of first-cousin marriages among parents of EOCA patients (4.5%) was lower than expected using the Dahlberg formula (8.9%).