Clinical and pathological features of a parkinsonian syndrome in a family with an Ala53Thr α‐synuclein mutation

Abstract We describe an Australian family of Greek origin with a parkinsonian syndrome and an Ala53Thr α‐synuclein gene mutation. Five of 9 siblings were affected, the average age of onset was 45 years, and the initial symptoms were variable, including resting tremor, bradykinesia, and gait disturbance, as previously described in families with the same point mutation. Affected family members responded well to levodopa, developed progressive cognitive impairment, and had a disease duration of 5 to 16 years. Pathologic features typical of idiopathic Parkinson's disease were found at autopsy. However, there were several additional features not previously reported in families with this gene mutation. These features included severe central hypoventilation, orthostatic hypotension, prominent myoclonus, and urinary incontinence. An abundance of α‐synuclein–immunoreactive Lewy neurites were found in the brainstem pigmented nuclei, hippocampus, and temporal neocortex. The Lewy neurites were associated with temporal lobe vacuolation. Subcortical basal ganglia cell loss and gliosis were seen. These additional clinical and pathological features suggest that the Ala53Thr α‐synuclein mutation can produce a more widespread disorder than found in typical idiopathic Parkinson's disease. Ann Neurol 2001;49:313–319