Profile of families with parkinsonism‐predominant spinocerebellar ataxia type 2 (SCA2)

Abstract

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.

Parkinsonism, FXTAS, and FMR1 premutations

“…Phenotypic overlap between PD and other neurodegenerative diseases, including some spinocerebellar ataxias particularly with SCA2 and SCA3 mutations and frontotemporal dementia with parkinsonism linked to chromosome 17, has been demonstrated. [15][16][17] The phenotype of FXTAS does not seem to overlap with PD, at least not when patients are diagnosed by neurologists using standard diagnostic criteria for PD. This finding is supported by the fact that the fragile X premutation was not found in any of the PD or atypical parkinsonism patients in our sample.…”

Genetic and clinical analysis in a Chinese parkinsonism-predominant spinocerebellar ataxia type 2 family

“…10,11 Although some parkinsonism clinical signs such as dystonia and tremor have been described in SCA2, dopamine-responsive parkinsonism has been infrequently described in SCA2 (see ref. 12). The sign of dopamine-responsive just has been seen in some Chinese families 13,14 and some white families.…”

The relationship between restless leg syndrome and 25-hydroxy D vitamin in hemodialysis patients

“…These results support the relationship of abnormal dopaminergic transmission diseases such as schizophrenia and Parkinson's disease with vitamin D [20]. It was reported in an in-vitro study that the increasing intense expression of vitamin D receptors in dopamine neurons in the brain, especially in the substantia nigra area increased the expression of tyrosine hydroxylase which is a rate-limiting enzyme in dopamine synthesis in adrenal medulla cells with the effect of 1.25 (OH) D2, D3 [21]. In addition, both vitamin D receptors and 1 alpha-hydroxylase enzyme are expressed in human brain, especially in substantia nigra neurons (probably dopaminergic) [22].…”