Abstract
OBJECTIVES: SLC6A1-related disorders encompass heterogeneous neuropsychiatric manifestations through GABAergic dysregulation, without any specific abnormalities on brain MRI, nor evidence of dopaminergic cell loss on I(123)-FP-β-CIT SPECT. We report here a case of globus pallidus lesions and dopaminergic denervation in a patient with a pathogenic SLC6A1 variant. METHODS: A 26-year-old female patient with intellectual disability, behavioral, and psychiatric disorders treated by neuroleptics for many years developed a parkinsonian syndrome associated with mild hand dystonia and chorea. A 3T brain MRI and I(123)-FP-β-CIT SPECT were performed. RESULTS: MRI of the brain found bilateral pallidal lesions consistent with neurodegeneration with iron accumulation. The I(123)-FP-β-CIT SPECT showed bilateral striatal presynaptic dopaminergic denervation. Whole-genome sequencing revealed a pathogenic SLC6A1 de novo variant. No additional variant was found in any of the genes responsible for Neurodegeneration with Brain Iron Accumulation (NBIA). DISCUSSION: This is a description of dopaminergic denervation and globus pallidus lesions with iron accumulation related to a SLC6A1 pathogenic variant. These findings expand the phenotype of SLC6A1-related disorder and suggest that it could be considered as a differential diagnosis of NBIA.