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

• Published in: Journal of neurology Vol. 265; no. 3; pp. 478 - 485
• Main Authors: Lin, Juei-Jueng, Lu, Chin-Song, Tsai, Chon-Haw
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2018; Springer Nature B.V
• Subjects: Aged; Brain diseases; Child; Computed tomography; Corpus Striatum - diagnostic imaging; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dihydroxyphenylalanine; Dopamine; Dopamine - metabolism; Dopamine receptors; Dopamine transporter; Dystonia; Dystonic Disorders - diagnostic imaging; Dystonic Disorders - drug therapy; Dystonic Disorders - genetics; Dystonic Disorders - metabolism; Family; Female; GTP Cyclohydrolase - genetics; Guanosine; Humans; Male; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Movement disorders; Mutation; Neostriatum; Neurodegenerative diseases; Neuroimaging; Neurology; Neuroradiology; Neurosciences; Original Communication; Parkinson's disease; Point mutation; Single photon emission computed tomography; Substantia Nigra - diagnostic imaging; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Tomography, Emission-Computed, Single-Photon; Parkinsonism; Brain; Dopamine transporter (DAT); Dopa-responsive dystonia (DRD); Guanosine triphosphate cyclohydrolase 1 (GCH-1) gene; Tc-TRODAT-1 SPECT imaging; Asymptomatic gene carrier; Brain 99mTc-TRODAT-1 SPECT imaging
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-017-8723-5

We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a
99m
Tc-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.