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Variability of presynaptic nigrostriatal dopaminergic function and clinical heterogeneity in a dopa-responsive dystonia family with GCH-1 gene mutation

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Abstract

We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a 99mTc-TRODAT-1 (TRODAT) scan in a dopa-responsive dystonia (DRD) family with the guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation. Clinically, there was presentation of intrafamilial variability in the DRD family. The index patient was a 10-year-old girl with classic DRD and normal presynaptic nigrostriatal dopaminergic function. However, her grandmother, a 79-year-old woman, presented with slowly progressive Parkinson’s disease (PD) without dystonic symptoms and excellent response to dopaminergic therapy for 21 years. Her brain TRODAT SPECT imaging revealed a markedly and asymmetrically reduced uptake of dopamine transporter at the bilateral striatum. Her father, a 54-year-old man, was an asymptomatic gene carrier and his brain TRODAT SPECT imaging revealed asymmetrically reduced nigrostriatal dopaminergic transmission in the bilateral striatum. We conclude variability of presynaptic nigrostriatal dopaminergic function in patients with DRD is related to their clinical heterogeneity. Significantly, impairment of presynaptic dopamine function actually occurs in the asymptomatic gene carrier.

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Authors and Affiliations

  1. Department of Neurology, Chushang Show-Chwan Hospital, No. 75, Sec. 2, Chi-Shang Rd, Chushang Jenn, 557, Nantou county, Taiwan, ROC

    Juei-Jueng Lin

  2. Department of Neurology, Chung-Shan Medical University Hospital, Taichung City, Taiwan, ROC

    Juei-Jueng Lin

  3. Department of Neurology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, ROC

    Chin-Song Lu

  4. Department of Neurology, China Medicine University Hospital, Taichung City, Taiwan, ROC

    Chon-Haw Tsai

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  1. Juei-Jueng Lin
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  3. Chon-Haw Tsai
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Correspondence to Juei-Jueng Lin.

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Lin, JJ., Lu, CS. & Tsai, CH. Variability of presynaptic nigrostriatal dopaminergic function and clinical heterogeneity in a dopa-responsive dystonia family with GCH-1 gene mutation. J Neurol 265, 478–485 (2018). https://doi.org/10.1007/s00415-017-8723-5

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  • DOI: https://doi.org/10.1007/s00415-017-8723-5

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