biostudies-literatureAdang LANational Institute of Neurological Disorders and StrokeNICHD NIH HHSNINDS NIH HHS374-386https://www.ebi.ac.uk/biostudies/studies/S-EPMC10947943biostudies-literatureUnknown47(2)Sulfatases catalyze essential cellular reactions, including degradation of glycosaminoglycans (GAGs). All sulfatases are post-translationally activated by the formylglycine generating enzyme (FGE) which is deficient in multiple sulfatase deficiency (MSD), a neurodegenerative lysosomal storage disease. Historically, patients were presumed to be deficient of all sulfatase activities; however, a more nuanced relationship is emerging. Each sulfatase may differ in their degree of post-translational modification by FGE, which may influence the phenotypic spectrum of MSD. Here, we evaluate if residual sulfatase activity and accumulating GAG patterns distinguish cases from controls and stratify clinical severity groups in MSD. We quantify sulfatase activities and GAG accumulation using three complJournal of inherited metabolic diseaseBiochemical signatures of disease severity in multiple sulfatase deficiency.PMC10947943K08NS105865U54NS115052K23NS114113K08 NS105865K23 NS114113R21HD106348R21 HD106348U54 NS115052Adang LAHerbst ZMBentley BRadhakrishnan KVanderver AYu EZhou ZDe Castro MPham VPillai NRSchlotawa LOrchard PJGelb MHMowafy SAhrens-Nicklas RCPasquali MfalseBiochemical signatures of disease severity in multiple sulfatase deficiency.Sulfatases catalyze essential cellular reactions, including degradation of glycosaminoglycans (GAGs). All sulfatases are post-translationally activated by the formylglycine generating enzyme (FGE) which is deficient in multiple sulfatase deficiency (MSD), a neurodegenerative lysosomal storage disease. Historically, patients were presumed to be deficient of all sulfatase activities; however, a more nuanced relationship is emerging. Each sulfatase may differ in their degree of post-translational modification by FGE, which may influence the phenotypic spectrum of MSD. Here, we evaluate if residual sulfatase activity and accumulating GAG patterns distinguish cases from controls and stratify clinical severity groups in MSD. We quantify sulfatase activities and GAG accumulation using three compl2024-01-01T00:00:00Z2024 Mar2026-06-01T18:00:15.818Z2025-04-04T00:12:14.838ZS-EPMC109479433787098610.1002/jimd.12688