A Novel Multimodal <scp>LC</scp> – <scp>MS</scp> / <scp>MS</scp> Panel for the Comprehensive Diagnosis of Neurometabolic Disorders in <scp>CSF</scp>

metabolites, with significantly reduced sample volume and measurement time. Due to their different biochemical interactions several runs with different sample preparation, running time and columns are necessary within the LC-MS/MS. Age-dependent reference values have been established. Positive controls with consistently detectable metabolite patterns were used to assess analytical reliability. The method has been implemented into routine diagnostics practice. The LC-MS/MS panel enables a simple, comprehensive, and rapid diagnostic approach, reducing time to diagnosis and facilitating early initiation of treatment. Instead of 650 μL, only 250 μL CSF is now required and the analysis time for all metabolites is reduced from 280 to 65.3 min excluding preparation and setup time. Furthermore, the panel is adaptable and can be regularly expanded to include additional clinically relevant metabolites. The novel LC-MS/MS panel, together with a neurometabolomic approach, offers a promising avenue to timely clinical diagnosis. Trial Registration: German Clinical Trials Register: DRKS00007878.