Objective: To report a patient with a novel mutation of GCH1 gene presenting as dopa-responsive dystonia (DRD), parkinsonism, and oculogyric crises (OGC)

Background: Autosomal dominant DYT/PARK-GCH1 is the most common form of DRD, typically presenting with early-onset lower limb dystonia, an excellent response to levodopa, and diurnal fluctuations. The OGC has been rarely reported in patients with DYT/PARK-GCH1.

Method: Case report

Results: A 50-year-old daughter and a 75-year-old mother presented to the clinic. The mother complained of recurrent episodes of symptoms including reduced facial expression, speech disturbance, drooling, heavy eyelids, and resting tremors since 10 years ago. Her symptoms lasted for a month during the transitional period between seasons. Neurological examinations showed hypomimia, bradykinesia, rigidity, and 4 Hz, moderate amplitude of resting tremors in both hands, worse on the right side. She walked slowly with short steps, the right leg was dragged, and both arm swings were reduced. There was no dystonia.
The daughter had severe generalized tremors once every two years from her age of 24, which showed notable diurnal fluctuation with aggravation toward the late afternoon or evening. Tremor was accompanied with a prolonged involuntary upward deviation of the eyes. Neurological examinations showed bradykinesia and sustained, 4 Hz, moderate amplitude of resting tremors in both limbs, worse on the left side. She showed inversion of the feet and flexion of the toes during gait. Considering leg dystonia, tremor-dominant parkinsonism with recurrent history of OGC, and diurnal fluctuation of symptoms, DRD was tentative diagnosis.
Dopamine transporter uptakes were preserved in both patients. A small dose of levodopa (200mg a day) improved symptoms absolutely in a daughter and partially in her mother. Genetic analysis found a novel heterozygous likely pathogenic variant c.605T>G (p.V202G) in exon 5 of GCH1 gene in both of them.

Conclusion: We highlights intra-familial phenotypic variability in DYT/PARK-GCH1 from a daughter with DRD, parkinsonism, and OGC and her mother with late-onset fluctuating parkinsonism. The OGC is a rare but distinctive clinical sign leading into the appropriate diagnostic context of hypo-dopaminergic state. To our knowledge, this is the first case report of autosomal-dominant DYT/PARK-GCH1 with a novel mutation presenting as DRD with OGC.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-mutation-of-gch1-gene-in-a-case-of-dopa-responsive-dystonia-with-oculogyric-crises/