Defective MPI causes MPI-CDG

Mannose 6-phosphate isomerase (MPI) normally isomerises fructose 6-phosphate (Fru6P) to mannose 6-phosphate (Man6P) in the cytosol. Man6P is a precursor in the synthesis of GDP-mannose and dolichol-phosphate-mannose, required for mannosyl transfer reactions in the N-glycosylation of proteins. Defects in MPI cause congenital disorder of glycosylation 1b (MPI-CDG, previously known as CDG1b,; MIM:602579), a multisystem disorder characterised by under-glycosylated serum glycoproteins. Unlike PMM2-CDG (CDG1a), there is no neurological involvement with MPI-CDG. Instead, patients present predominantly with diarrhoea, failure to thrive and protein-losing enteropathy. MPI-CDG is one of two CDGs that can be treated with oral mannose supplementation, but can be fatal if left untreated.

Summary from Reactome (R-HSA-4043916), read 2026-09-23.