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GLUD1 mutations reduce the sensitivity of the enzyme to its inhibitor GTP, which fuels hyperinsulinaemia/hyperammonaemia (HI/HA) syndrome, a condition characterized by elevated blood NH4 + levels and low glucose levels (MacMullen et al., 2001)

[DOI] [PMC free article] [PubMed] [Google Scholar] 131.Jacka F.N., Pasco J.A., Mykletun A., Williams L.J., Hodge A.M., OReilly S.L., Nicholson G.C., Kotowicz M.A., Berk M

However, clinical translation remains limited by off-target effects, bloodbrain barrier challenges and variability in pathway regulation

Clinical markers of progression Older age, male sex, higher baseline motor scores and worse baseline cognition have all been linked to worse motor and cognitive outcomes at longitudinal follow-up 141,182,194,195,196 and have been integrated with sleep disorder, presence of depression and various genetic, imaging or CSF biomarkers into clinical predictive scores 182,196