Objective: To report a case of tyrosine hydroxylase deficiency (THD), a rare neurometabolic disorder that disrupts catecholamine biosynthesis. This case report highlights common neurologic abnormalities, diagnostic challenges, and therapeutic considerations.

Background: Tyrosine hydroxylase (TH)catalyzes the rate-limiting step for dopamine synthesis. THD is a rare genetic disorder that has a wide spectrum of clinical features, including developmental delays (cognitive, motor, and speech), movement disorders (dystonia and parkinsonism), and autonomic dysfunction.

Method: A 39-year-old-woman with spastic diplegia, dystonia, tremors, and intellectual delay presented to our movement disorders clinic to establish care. She experienced generalized dystonia since birth with no history of trauma or prenatal health issues. Over time, she developed progressive motor, speech, cognitive, and psychiatric symptoms. Her movement symptoms (including muscle spasms, generalized dystonia, and parkinsonism) were partially alleviated by carbidopa-levodopa and pyridostigmine since childhood, alongside rehabilitative services.

Results: Previous imaging and laboratory studies failed to explain her symptoms. Additionally, she had family history of myopathy and dystonia in her mother and sister; thus, medical workup also included nuclear and mitochondrial DNA sequencing but no conclusive diagnosis was made. Due to her early-onset movement disorders and family history, a genetic panel for movement disorders was ordered. The results revealed mutations in the TH gene, including one pathogenic variant and a variant of unknown significance. Based on her clinical history, family history, and responsiveness to carbidopa-levodopa, the genetic mutations confirmed the diagnosis of tyrosine hydroxylase deficiency (THD) and provided an explanation for the patient’s complex neurological symptoms.

Conclusion: The rarity and clinical variability of THD makes the diagnosis challenging. However, the availability and utilization of specialized genetic panels can significantly improve diagnostic yield and ultimately improve patient outcomes. The cornerstone of management for motor symptoms involves treating dopamine deficiency with levodopa and dopamine agonists. Additionally, long-term management should include rehabilitative services, neuropsychiatric treatments, and autonomic symptoms management.

References: 1. Bondarenko, M. S., Kuseyri Hübschmann, O., Kulhánek, J., Pons, R., Pearson, T. S., Jeltsch, K., Badnjarevic, I., Wassenberg, T., Horvath, G., Stevanovic, G., Kurian, M. A., Cortès-Saladelafont, E., Roubertie, A., Leuzzi, V., Bertoldi, M., Mastrangelo, M., Assmann, B., THD Guidelines Working Group, Garcia-Cazorla, A., & Opladen, T. (2025). Consensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase (TH) Deficiency. Journal of inherited metabolic disease, 48(6), e70106. https://doi.org/10.1002/jimd.70106
2. Kumar, A., Devarajan, R., & Ramesh, S. (2015). Genetic mechanisms in movement disorders: New insights into THD-related dystonia. Journal of Movement Disorders, 8(2), 57–64. https://doi.org/10.14802/jmd.15028
3. Stamelou, M., Edwards, M. J., & Bhatia, K. P. (2013). The management of dystonia in movement disorders. Current Treatment Options in Neurology, 15(3), 348–361. https://doi.org/10.1007/s11940-013-0220-7
4. Tassin, M. T., & Navarro, J. (2020). Tyrosine hydroxylase deficiency: From the bench to the bedside. Movement Disorders Clinical Practice, 7(2), 135–141. https://doi.org/10.1002/mdc3.12889

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MDS Abstracts - https://www.mdsabstracts.org/abstract/thd-tyrosine-hydroxylase-deficiency-in-a-39-year-old-woman-with-early-onset-dystonia/