Gene PMM2
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Also known as
CDG1A, Phosphomannomutase 2Overview
PMM2 (Phosphomannomutase 2) encodes an essential enzyme in the glycosylation pathway that catalyzes the conversion of mannose-6-phosphate to mannose-1-phosphate. This enzymatic step is crucial for the synthesis of GDP-mannose, which serves as a sugar donor for N-glycosylation of proteins. Proper protein glycosylation is vital for normal protein folding, stability, trafficking, and function throughout the body. The PMM2 enzyme is particularly important during development and in tissues with high protein synthesis rates.Mutations in PMM2 cause PMM2-congenital disorder of glycosylation (PMM2-CDG, formerly known as CDG-Ia), which is the most common congenital disorder of glycosylation. This autosomal recessive condition affects multiple organ systems and presents with a wide spectrum of severity, from severe multisystem disease in infancy to milder neurological manifestations. Common features include developmental delay, cerebellar hypoplasia, abnormal fat distribution, inverted nipples, and coagulation abnormalities. The clinical presentation varies depending on residual enzyme activity, with some mutations allowing for milder phenotypes. Currently, there is no specific cure, and treatment is primarily supportive and symptomatic.