Psychotic symptoms in tyrosine hydroxylase deficiency-associated dopa-responsive dystonia treated with antipsychotics...

Tyrosine hydroxylase deficiency (THD) is a rare autosomal recessive disorder caused by mutations in the TH gene. THD encompasses a broad phenotypic spectrum that includes dopamine-responsive dystonia (DRD) as its milder presentation, alongside severe infantile parkinsonism and progressive infantile encephalopathy. Although non-motor manifestations-such as depression, anxiety, and sleep disturbances-have garnered increasing attention, psychotic symptoms including hallucinations and delusions remain rarely reported in THD.

This report describes a genetically confirmed woman with THD who presented with infantile-onset dystonia. Auditory hallucinations and erotomanic delusions emerged approximately five years after levodopa initiation and persisted despite one-month levodopa withdrawal. Although levodopa markedly improved her dystonia, antipsychotic treatment posed a therapeutic dilemma: risperidone exacerbated motor symptoms, and aripiprazole was limited by poor adherence. A multimodal regimen comprising aripiprazole, quetiapine, and low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left temporoparietal cortex was associated with progressive improvement of psychotic symptoms without clinically apparent worsening of dystonia. The independent contribution of rTMS could not be determined given the concurrent pharmacological titration.

Selecting appropriate antipsychotic medication in THD patients with prominent psychotic symptoms poses a considerable challenge. The combination of aripiprazole, quetiapine, and rTMS may represent a potential therapeutic option. To our knowledge, this is the first reported case of genetically confirmed DRD due to THD presenting with prominent psychotic symptoms, and among the few documenting rTMS use in this population. These observations are based on clinical assessment without standardized quantitative measures; the independent efficacy of rTMS cannot be established from this case.