In our previous work on DTDS, the postulated disease mechanism is loss of dopamine re-uptake, which leads to depleted presynaptic dopamine stores and excessive extraneuronal dopamine, which may also overstimulate presynaptic D2 autoreceptors leading to inhibition of tyrosine hydroxylase and subsequently reduce dopamine production (Blackstone, 2011). Here, TH is linked to SLC6A3-related dopamine transporter deficiency syndrome.