Objective: To explore the clinical and genetic characteristics of children with
dopa-responsive dystonia (DRD) caused by
tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal
hypotonia (8 cases), limb
muscle hypotonia (7 cases),
hypokinesia (6 cases), decreased facial expression (4 cases),
tremor (3 cases),
limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb
muscle hypertonia (1 case) and
drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal
hypotonia, oculogyric crises, status dystonicus,
hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants,
3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well
as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by
levodopa and
benserazide hydrochloride
tablets and 1 severe patient was treated by
levodopa tablets. All the severe patients responded well to
levodopa and
benserazide hydrochloride
tablets or
levodopa tablets. Although the weight of the patients increased and the
drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed
dyskinesia in the early stage of treatment with
levodopa and
benserazide hydrochloride
tablets and it disappeared after
oral administration of
benzhexol hydrochloride
tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving
levodopa and
benserazide hydrochloride
tablets for only 2 months. The very severe patient was extremely sensitive to
levodopa and
benserazide hydrochloride
tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to
levodopa and
benserazide hydrochloride
tablets or
levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the
drug dosage, and no obvious side effect is observed.