Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: We aim to describe clinical phenotype, genotype and functional studies in a new cohort patients identified with Dopamine Transporter deficiency syndrome (DTDS).
Background: Dopamine transporter deficiency syndrome (DTDS) is a monogenic neurotransmitter disorder that presents with a progressive infantile onset parkinsonism-dystonia movement disorder. It is characterized by raised CSF homovallinic acid: 5-hydroxyindoleacetic acid (HVA: HIAA) ratio. It is caused by pathogenic mutations in the SLC6A3 gene that encode for the dopamine transporter (DAT).
Methods: Children presenting with infantile parkinsonism-dystonia associated with a raised CSF HVA: HIAA > 4 were identified. Mutational analysis for SLC6A3 gene that encodes for DAT was performed in all cases with in vitro functional studies where appropriate.
Results: Three patients were identified with a history of classical infantile onset parkinsonism dystonia movement disorder. One case responded to pimozidine treatment for hyperkinesia whilst the others did not respond to any pharmacotreatments tried. All habor novel,previously undescribed missense mutations in SLC6A3 gene (2 compound heterozygous: 1 homozygous). In vitro functional studies demonstrated reduced dopamine uptake with reduced binding affinity, surface binding and dopamine recognition. Immunoblotting studies showed absence or reduced glycosolated DAT expression.
Conclusions: We present a new cohort of classical DTDS patients with novel mutations in SLC6A3 gene. Functional analysis studies have characterised impaired dopamine uptake, binding affinity and surface binding. The invitro functional analysis further confirm previous data that all classical infantile onset DTDS missense mutations studied to date retain dopamine uptake of below 5% and may help predict phenotypic disease severity and prognosis. DTDS remains underrecognised and the phenotypic spectrum is expanding with disease severity related to residual dopamine uptake activity. Therefore DTDS should now be considered as a cause for cerebral palsy mimics, juvenile parkinsonism-dystonia, and early onset Parkinson’s disease.
To cite this abstract in AMA style:J. Ng, J. Zhen, K. Erreger, N.C. Oien, S. Mohammed, J.P. Linn, J. Muntadas, I. Denzler, A. Garcia Cazorla, R. Artuch, S. Pope, S.J.R. Heales, A. Galli, M.E.A. Reith, M.A. Kurian. Novel mutations identified in dopamine transporter deficiency syndrome [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/novel-mutations-identified-in-dopamine-transporter-deficiency-syndrome/. Accessed September 25, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-mutations-identified-in-dopamine-transporter-deficiency-syndrome/