Objective: To explore the possible relationship between tyrosine hydroxylase deficiency (THD) and absence epilepsy, with a specific focus on the role of dopamine in the modulation of thalamocortical circuits.

Background: THD is a rare autosomal recessive disorder affecting dopamine biosynthesis, causing movement disorders (dystonia, parkinsonism, and other motor delays), autonomic dysfunction, and intellectual disability. The relationship between THD and epilepsy remains poorly understood. Absence epilepsy is thought to result from dysregulation of thalamocortical circuits. Emerging evidence suggests that dopamine plays a critical role in modulating neuronal excitability within these circuits. This raised the possibility that dopaminergic dysfunction in THD may contribute to epileptogenesis.

Method: The study utilized a case report approach to investigate the relationship between THD and absence epilepsy.

Results: This case describes a rare association between THD and epilepsy in a 16-year-old boy with significant psychomotor developmental delay. Hypotonia was first noticed within the first six months of life. At four months of age, oculogyric crises were observed. He also exhibited delayed motor development, truncal hypotonia, limb hypertonia, oculogyric crises, and intellectual disability. Genetic testing confirmed a mutation in the tyrosine hydroxylase (TH) gene. Levodopa treatment was initiated, but the patient experienced severe dyskinesias, limiting its use. At 12 years of age, levodopa was reintroduced at a low dose (100 mg per day), divided into small doses every 2–3 hours. At 13 years of age, he developed absence seizures, characterized by a 3-Hz spike-and-wave pattern on EEG. Valproic acid was initiated, leading to partial seizure control. Better seizure control was achieved when the levodopa dose was increased, suggesting a possible role of dopaminergic modulation in seizure susceptibility.

Conclusion: This case report supports the hypothesis that the hypodopaminergic state in THD may alter thalamocortical circuit dynamics, predisposing individuals to generalized seizures. Dopamine’s modulatory role in thalamic excitability and its interaction with GABAergic systems are crucial in regulating neuronal activity and seizure propagation.

References: 1. Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDS Gene Review.Weissbach A, Pauly MG, Herzog R, et al. Movement Disorders : Official Journal of the Movement Disorder Society. 2022;37(2):237-252. doi:10.1002/mds.28874.
2. Altered Neurotransmitter Expression in the Corticothalamocortical Network of an Absence Epilepsy Model With Impaired Feedforward Inhibition. Adotevi N, Su A, Peiris D, Hassan M, Leitch B. Neuroscience. 2021;467:73-80. doi:10.1016/j.neuroscience.2021.05.024.
3. Early Reduced Dopaminergic Tone Mediated by D3 Receptor and Dopamine Transporter in Absence Epileptogenesis. Cavarec F, Krauss P, Witkowski T, et al. Epilepsia. 2019;60(10):2128-2140. doi:10.1111/epi.16342.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tyrosine-hydroxylase-deficiency-and-absence-epilepsy-an-association-or-mere-coincidence/