GCH-1 genetic variant may cause Parkinsonism by unmasking the subclinical nigral pathology

Background Recent studies suggest that GTP cyclohydrolase 1 (GCH-1) variant may be a risk factor for nigral degeneration causing PD. Methods A 49-year-old Korean woman visited our movement disorder clinic with the initial presentation of Parkinsonism starting at age 47. We monitored the degree of nigral degeneration with serial FP-CIT PET throughout the course of her disease (2, 8 and 11 years from disease onset). Results The initial clinical presentation was consistent with intrinsic dopamine deficiency caused by GCH-1 variant. However, her follow-up disease course was consistent with Parkinsonism caused by nigral neurodegeneration. We found a novel GCH-1 variant in the current case. The disease course of the patient was overall benign in motor and non-motor aspects, corresponding to previously reported GCH-1 cases with PD. Serial FP-CIT PET scans showed normal initial FP-CIT binding followed by a continuous decline of the putaminal binding ratio. However, the decreased binding ratio could not sufficiently explain the corresponding clinical duration of the patient. Therefore, dopamine deficiency by GCH-1 genetic variant contributed to Parkinsonism in the current case with subclinical nigral degeneration. Conclusion Our case suggests that GCH-1 variant causes Parkinsonism by unmasking the subclinical nigral pathology, not by causing the nigral neurodegeneration.