Objective: We report a case presenting with symptoms of classical Dopamine Transporter Deficiency Syndrome (DTDS) with negative results on initial whole-exome sequencing (WES), but eventually positive for SLC6A3 mutation on repeat analysis and confirmed with DaTScan.

Background: SLC6A3-related DTDS typically presents in infancy as a heterogeneous movement disorder with chorea, dystonia, dystonia-parkinsonism, ballismus, or orolingual dyskinesia. Secondary orthopedic, gastrointestinal, and respiratory complications are common. Atypical DTDS has a delayed onset of these symptoms preceded by a normal childhood. In addition to biallelic pathogenic variants in SLC6A3 on gene testing, a DatScan rarely used in pediatric population can be highly suggestive if it shows diminished tracer uptake in the basal ganglia.

Method: Case report

Results: A 14-year-old male with global developmental delays, generalized dystonia, tremor, bulbar dysfunction, and parkinsonism since infancy. He received a diagnosis of cerebral palsy initially while undergoing evaluation including brain MRI, MRS, EEGs, mitochondrial, metabolic, genetic causes, cerebral palsy, brain metal accumulation disorders, were unremarkable. Given his age of onset and progression of symptoms, his phenotype fit more with the classical DTDS, however, WES initially reported as negative. No episodes of status dystonicus, ocular manifestations, orolingual dyskinesias, or pulmonary complications over the years. 

Re-analysis of WES showed 2 variants in the SLC6A3 gene, 1 pathogenic (maternally inherited) and another variant of uncertain significance (paternally inherited). Due to his possible diagnosis of SLC6A3-DTDS with some atypical features, DaTScan was completed which showed virtually absent uptake in bilateral putamen and caudate nuclei. A re-review of CSF neurotransmitters from 2009 revealed a CSF HVA:5-HIAA ratio >4.0 further suggestive of this disorder. Treatment has been focused symptomatically on dystonia with baclofen and dopamine agonists and management of secondary orthopedic and gastrointestinal complications.

Conclusion: DTDS is a rare disorder, can mimic various movement disorders and should be thoroughly investigated in progressive childhood movement disorders, atypical dystonic/spastic cerebral palsy and early-onset Parkinsonism. DaTScan are rarely used in the pediatric population, but its clinical utility should be considered in rare cases to support diagnoses.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/diagnostic-challenges-in-a-case-of-slc6a3-related-dopamine-transporter-deficiency-syndrome/