Movement disorders clinical practice · 2025
Phenotypic, Genotypic Characteristics, and Treatment Strategies of Pediatric Tyrosine Hydroxylase Deficiency: A Single-Center Retrospective Analysis of 51 Cases.
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Ban Tingting, Cheng Ye, Zhang Yan, Lin Caimei, Chai Yiming, Li Wenhui, Zhang Linmei, Xing Qinghe, Wang Yi, Zhou Shuizhen
Аннотация
BACKGROUND: Tyrosine hydroxylase deficiency (THD) is a rare autosomal recessive disorder caused by impaired catecholamine biosynthesis in the brain. The rarity and heterogeneous clinical spectrum of THD often lead to misdiagnosis, and evidence-based, genotype-specific levodopa dosing protocols remain unavailable.
OBJECTIVE: To delineate the clinical spectrum, genetic variants, and levodopa response in a large single-center cohort of Chinese pediatric THD patients, and to explore genotype-specific dosing requirements.
METHODS: A retrospective analysis was performed on 51 pediatric patients diagnosed with THD at a single center in China. Data on genotype, phenotype, and treatment outcomes were reviewed.
RESULTS: Movement disorders were present in 96.1% of cases, with developmental delay observed in 88.2%, and autonomic symptoms in 51.0%. Among the 36 identified variants, the predominant were p.R233H (37.3%), p.R153X (10.8%), and p.Q232X (6.9%). Among the 13 p.R233H carriers who showed a good response to levodopa, those with a nonsense second allele (n = 5) required a significantly higher mean levodopa dose than those with a missense second allele (n = 8) (P = 0.03).
CONCLUSIONS: This study is the largest retrospective analysis of pediatric THD patients from a single-ethnicity cohort, summarizing the clinical and genotypic characteristics. Variant type-particularly R233H/nonsense versus R233H/missense significantly influences dose requirements, underscoring the value of genotype-guided, dynamic levodopa titration to optimize long-term outcomes.
OBJECTIVE: To delineate the clinical spectrum, genetic variants, and levodopa response in a large single-center cohort of Chinese pediatric THD patients, and to explore genotype-specific dosing requirements.
METHODS: A retrospective analysis was performed on 51 pediatric patients diagnosed with THD at a single center in China. Data on genotype, phenotype, and treatment outcomes were reviewed.
RESULTS: Movement disorders were present in 96.1% of cases, with developmental delay observed in 88.2%, and autonomic symptoms in 51.0%. Among the 36 identified variants, the predominant were p.R233H (37.3%), p.R153X (10.8%), and p.Q232X (6.9%). Among the 13 p.R233H carriers who showed a good response to levodopa, those with a nonsense second allele (n = 5) required a significantly higher mean levodopa dose than those with a missense second allele (n = 8) (P = 0.03).
CONCLUSIONS: This study is the largest retrospective analysis of pediatric THD patients from a single-ethnicity cohort, summarizing the clinical and genotypic characteristics. Variant type-particularly R233H/nonsense versus R233H/missense significantly influences dose requirements, underscoring the value of genotype-guided, dynamic levodopa titration to optimize long-term outcomes.