Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy

Type 1 Gaucher disease (GD1), a glycosphingolipid storage disorder caused by deficient activity of lysosomal glucocerebrosidase, is classically considered non‐neuronopathic. However, current evidence challenges this view. Multiple studies show that mutations in GBA1 gene and decreased glucocerebrosidase activity are associated with increased risk for Parkinson disease. We tested the hypothesis that subjects with GD1 will show neurochemical abnormalities consistent with cerebral involvement. We performed Magnetic Resonance Spectroscopy at 7 T to quantify neurochemical profiles in participants with GD1 (n = 12) who are on stable therapy. Age and gender matched healthy participants served as controls (n = 13). Neurochemical profiles were obtained from parietal white matter (PWM), posterior cingulate cortex (PCC), and putamen. Further, in the GD1 group, the neurochemical profiles were compared between individuals with and without a single L444P allele. We observed significantly lower levels of key neuronal markers, N‐acetylaspartate, γ‐aminobutyric acid, glutamate and glutamate‐to‐glutamine ratio in PCC of participants with GD1 compared to healthy controls (P