Purpose or Case Report: 3-year-old female with history of Aromatic l-amino acid decarboxylase (AADC) deficiency presented for direct intra-putaminal Dopa decarboxylase (DDC) gene therapy infusion.
Pre-therapy 18F-DOPA PET brain study fused to MRI demonstrates absence of normal radiotracer uptake in the basal ganglia/putamen, consistent with history of AADC deficiency and inability to uptake and convert 18F-DOPA to 18F fluorodopamine. MRI Brain demonstrates normal appearance of the putamen. Intraoperative images from intra-putaminal DDC gene therapy infusion via a frame-based stereotactic approach. Following frame placement, 4 gene vectors delivered in a adeno-associated viral vector are infused to the putamen bilaterally. Intraoperative T2 Axial MRI confirms appropriate localization with increased signal seen in the anterior and posterior aspects of the putamen bilaterally. Post-therapy 18F-DOPA PET brain study, fused to MRI 10 weeks following intraputaminal infusions of the DDC genes coding for AADC, demonstrates development of robust 18F-DOPA uptake in the putamen, indicative of successful AADC production following gene therapy.
AADC enzyme deficiency is a debilitating autosomal recessive disease due to a mutation in the Dopa decarboxylase gene (DDC). Subsequent dopamine deficiencies result in profound motor and autonomic dysfunction, developmental delay and early mortality. Mean age of diagnosis is 3.5 years, severe cases often die before age 7. While currently no cure, novel gene therapy treatments utilizing direct infusion of the DDC gene into the basal ganglia/putamen have shown promising clinical results. While anatomic imaging such as MRI are typically normal, 18F-DOPA PET scans measure the uptake of the tracer and its conversion to 18F-fluorodopamine, indicating appropriate DDC function in the basal ganglia dopaminergic nerve terminals. 18F-DOPA PET scans can be used to assess the efficacy of gene therapy by demonstrating the successful development of striatal uptake prior to improvement of clinical symptoms.
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