Dopamine Transporter Deficiency Syndrome (DTDS)

Dopamine transporter deficiency syndrome (DTDS) associated with SLC6A3 is a complex and unusual form of movement disorder caused by human dopamine transporter (DAT) encoding variants of the SLC6A3 gene and characterized by progressive (worsening) dystonia and parkinsonism (Ng et al. 2023). DTDS is an autosomal recessive and multifaceted motor neurological condition with a spectrum ranging from typical early-onset (first 6 months) DTDS to atypical later-onset (in childhood or adulthood) DTDS (Ng et al. 2023). The affected individuals display hyperkinetic movements with dyskinesia (either orolingual and limb or both), choreiform movements, and dystonia or hypokinetic movements (typical Parkinsonian-like characteristics). Additional symptoms can include hypotonia, signs of the pyramidal tract, and eye coordination defects (Ng et al. 2023; Yildiz et al. 2017). There are two phenotypes of the disorder with interrelating clinical features: typical early-onset DTDS and atypical later-onset DTDS. Classic DTDS typically starts with few non-specific symptoms during early childhood, such as axial hypotonia, hyperkinetic motion disorders (orolingual dyskinesia chorea and dystonia), and oculomotor defects (Yildiz et al. 2017). Typically, the affected individuals often developed severe dystonia-parkinsonism over time, further complicated more by the occurrence of recurrent movement disorders and oculomotor irregularities. Contrary, during infancy and early adolescence, patients with atypical DTDS fulfill normal developmental targets. Nonetheless, in later stages such as childhood, adolescence, or adulthood, behavioral symptoms and a variety of movement disorders can develop over time, including rest tremor, action tremor, slurred or slow speech (dysarthria), and uncontrolled muscle contractions (dystonia) (Ng et al. 2023; Kurian and Assmann 2015). Classic DTDS is associated with poor outcomes, and death can occur in adolescents due to sudden ambiguous events or respiratory complications; however, those with atypical DTDS could have fewer complications and longer life expectancy; although, this form is not well known in the long-term (Ng et al. 2023; Yildiz et al. 2017; Kurian and Assmann 2015).