Autonomic Dysfunction in the Fragile X Associated Tremor/Ataxia Syndrome (PD2.007)

OBJECTIVE: To examine for the presence of autonomic symptoms among male FMR1 premutation carriers compared to published estimates of the same in healthy controls using the SCOPA-AUT. BACKGROUND: Fragile X- associated tremor ataxia syndrome (FXTAS) is caused by a trinucleotide expansion of a CGG repeat in the FMR1 gene on the X chromosome. Its clinical hallmarks are intention/action tremor, ataxia, parkinsonism and cognitive dysfunction. Autonomic dysfunction has also been suggested in some studies but remains to be established. DESIGN/METHODS: 56 FMR1 premutation carriers were recruited from an ongoing study at Emory University. Carriers underwent an abbreviated neurologic exam and completed the SCOPA-AUT. They were also administered motor scales for tremor, ataxia, parkinsonism, and the Montreal Cognitive Assessment battery (MOCA). SCOPA-AUT results were compared against those published in controls, and in patients with Parkinson Disease and Huntington Disease. RESULTS: FMR1 premutation carriers scored higher than published controls in the urinary symptoms subscale of the SCOPA-AUT (49 vs. 22, p FMR1 carriers had higher total SCOPA-AUT scores than HD subjects but lower than those of PD subjects. CONCLUSIONS: This data suggests that FMR1 premutation carriers have more urinary dysfunction than controls and HD patients, but not as much PD patients. It does not support a more generalized involvement of autonomic function. The correlation between urinary symptoms, motor and cognitive scores, raises the possibility that urinary symptomatology may be a marker of central neurodegeneration in FMR1carriers and FXTAS. Supported by: NIH grants R01 HD29909 and P30 HD24064. Disclosure: Dr. Lazarus has nothing to disclose. Dr. Allen has nothing to disclose. Dr. Shubeck has nothing to disclose. Dr. Sherman has nothing to disclose. Dr. Juncos has received personal compensation for activities with UCB Pharma, Novartis, and GlaxoSmithKline, Inc. Dr. Juncos has received research support from Novartis, Kyowa, Ovation Pharmaceuticals, Inc., and Eisai, Inc.