2026/04/06 by Stine Christ, Julia Rossmann, Sylvia Richter +6 · 1 voice
Neuroscience · Medicine · Biochemistry, Genetics and Molecular Biology · #Genetic Neurodegenerative Diseases #Epilepsy research and treatment #Metabolism and Genetic Disorders
paper · doi:10.1002/jimd.70167
openalex publication_date 2026/04/06 · openalex created_date 2026/04/07 · openalex updated_date 2026/07/22
ABSTRACT Metabolic testing of cerebrospinal fluid (CSF) is essential for early diagnosis of neurometabolic disorders. However, the large number of differential diagnoses, the phenotypic variance within a clinical picture, and the disease rarity complicate targeted metabolic diagnostics. To improve diagnosis the aim is to establish a liquid chromatography–tandem mass spectrometry (LC–MS/MS) based CSF panel (NeuroMetabolom) which enables a quick, reliable, extensive and cheap method requiring small amounts of analysis material replacing classical single platform analyses. The novel LC–MS/MS NeuroMetabolom method enables measuring all known standard metabolites in CSF, including purines/pyrimidines, sepiapterin, γ‐Aminobutyric acid (GABA), and vitamin B 6 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