Objective To investigate the strategy of diagnosis and treatment of dopa responsive dystonia-plus (DRD-plus) due totyrosine hydroxylase deficiency. Methods Nine patients with DRD-plus and onset in infancy treated in our hospital from October 2018 to July 2020 were retrospectively analyzed. Its clinical phenotype, TH gene encoding tyrosine hydroxylase, and efficacy of levodopa were analyzed.Results Nine patients developed the disease within 5. 5 months old. Seven cases (77. 8%) presented with severe infantile Parkinsonismsyndrome accompanied by delayed motor development. Two patients (22. 2%) presented with progressive infantile encephalopathy. All thepatients had complex heterozygous or homozygous variants of TH gene. A total of 12 variations of TH gene (10 missense variations and 1splice site variations) and one new variation (exon 9-11 deletion) were identified. p. R233H (33. 3%) was the most common variation. Aftertreatment with levodopa, 7 cases showed significant improvement in symptoms, but poor coordination in fine motor skills. Two cases with infantile encephalopathy were intolerant to the drug. They had difficulty in increasing the dosage of levodopa. They showed little improvementin symptoms, and suffered from severe intellectual and motor developmental delays and malnutrition. Conclusions Patients with severeDRD-plus caused by tyrosine hydroxylase deficiency have a relatively good prognosis. However, patients with infantile encephalopathy havedifficulty in increasing the dosage of levodopa. They have a poor prognosis.