Phenotypic, Genotypic Characteristics, and Treatment Strategies of Pediatric Tyrosine Hydroxylase Deficiency: A Single‐Center Retrospective Analysis of 51 Cases
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1002/mdc3.70371
Authors: Tingting Ban, Ye Cheng, Yan Zhang, Caimei Lin, Yiming Chai, Wenhui Li, Linmei Zhang, Qinghe Xing, Yi Wang, Shuizhen Zhou
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4415422263