Objective: To describe levodopa-responsive dystonia in ADSL deficiency and the use of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for refractory symptoms.

Background: ADSL deficiency is a rare autosomal recessive inborn error of purine metabolism associated with developmental delay and dystonia. No cases of ADSL-related dystonia treated with levodopa or DBS have been reported.

Method: We reviewed clinical, imaging, genetic, and treatment data in a pediatric patient with ADSL-related dystonia, including response to dopaminergic therapy and bilateral GPi DBS. Motor severity was assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).

Results: The patient presented in infancy with hypotonia, developmental delay, and progressive generalized dystonia. Genetic testing confirmed compound heterozygous pathogenic ADSL variants (p.Arg190Ter; p.Pro133Leu). Carbidopa/levodopa led to marked improvement in dystonia and assisted mobility. Over two years, he developed wearing-off motor fluctuations approximately four hours after dosing. Due to persistent fluctuations and functional impairment, bilateral GPi DBS was performed at age 13 without complications. Preoperative BFMDRS motor score OFF stimulation was 84 (April 2024). At 24-month follow-up, the BFMDRS motor score ON stimulation improved to 45 (March 2026), representing a 46% reduction in dystonia severity. Postoperatively, motor fluctuations stabilized with reduced wearing-off severity and decreased medication requirements. Caregivers reported improved head and neck control, reduced dystonic limb posturing, improved hand function with finger isolation and object grasp, and increased sitting tolerance. They estimated an overall improvement of 60-80%, along with improved sleep and reduced nocturnal dystonia requiring rescue medication.

Conclusion: This case demonstrates levodopa-responsive dystonia in ADSL deficiency and, to our knowledge, represents the first report of GPi DBS in this condition. Neuromodulation may be considered in selected refractory cases, though further study is needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-responsive-dystonia-in-adenylosuccinate-lyase-adsl-deficiency-treated-with-bilateral-gpi-deep-brain-stimulation/