Objective: Dopamine transporter deficiency syndrome (DTDS,) a rare disease characterized by infantile –onset progressive dystonia, has no established treatment guidelines.  Treatment is generally predicated on dystonia management, and most have been unresponsive to utilization of dopamine. Here we report 2 cases of DTDS treated with pharmacotherapy, botulinum toxin, and deep brain stimulation (DBS.)

Background: Both patients were noted to have generalized dystonia without spasticity as infants, with negative MRIs and unrevealing initial laboratory work-up.  Both were noted to have elevated homovanillic acid (HVA) in cerebrospinal fluid (MNG Laboratories) leading to their genetic evaluation and confirmed diagnosis (Kurian et al., 2009).  Patient A is a 13 year-old female, with parental consanguinity, with homozygous missense change in SLC6A3.  Patient B is a 14-year-old female without consanguinity and no significant neurologic family history, with spontaneous compound heterozygous mutations in SLC6A3.

Method: Two case reports.

Results: Subjective improvement in dyskinetic movements and irritability were appreciated by both families.  Treatment with levodopa and tetrabenazine yielded motor improvement in both patients. With continued progression of disease, both patients proceeded with DBS surgery. Patient A underwent DBS surgery in June 2015 with bilateral leads in the internal globus pallidus (GPi). Improvement of dystonia was seen.  Patient B underwent DBS surgery in February 2016 with bilateral leads placed in the GPi and ventral lateral (VLa) thalamus. Improvement of dystonia and resolution of tremulous movements was seen with DBS.

Conclusion: These two case reports suggest that DBS may prolong the life and improve the quality of life of children with DTDS, and the hyperkinetic movement seen in DTDS patients may be much improved with thalamic stimulation.  To our knowledge there have not been any other children with DTDS implanted with DBS.  These two cases demonstrate the importance of exploring avenues for treatment of symptoms in diseases we have yet to cure.

References: Kurian MA, Zhen J, Cheng SY, Li Y, Mordekar SR, Jardine P, Morgan NV, Meyer E, Tee L, Pasha S, Wassmer E, Heales SJ, Gissen P, Reith ME, Maher ER. Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. J Clin Invest. 2009;119:1595–603. Ng J, Zhen J, Meyer E, Erreger K, Li Y, Kakar N, Ahmad J, Thiele H, Kubisch C, Rider NL, Morton DH, Strauss KA, Puffenberger EG, D’Agnano D, Anikster Y, Carducci C, Hyland K, Rotstein M, Leuzzi V, Borck G, Reith ME, Kurian MA. Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood. Brain. 2014a;137:1107–19.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/two-patients-with-dopamine-transporter-deficiency-treated-with-deep-brain-stimulation/