PMM2-CDG (or CDG-1a) is a genetic metabolic disorder caused by a deficiency of cytosolic enzyme phosphomannomutase 2 (encoded by the gene PMM2), which is required for the conversion of mannose-6-phosphate to mannose-1-phosphate required for the synthesis of GDP-mannose, the donor of mannose to a growing lipid-linked oligosaccharide (LLO) precursor. As a result, the incorporation of mannose into LLO is reduced, and glycoproteins lacking complete N-linked glycans are synthesized.

Normal Proteins

Normal Cell

PMM2-CDG Proteins


The body’s failure to produce complete N-linked glycans causes highly variable clinical manifestations that may include feeding problems, vomiting, and diarrhea with failure to thrive in infants, and severe encephalopathy with axial hypotonia, abnormal eye movement, marked psychomotor retardation, peripheral neuropathy, cerebellar hypoplasia, stroke-like episodes, and retinitis pigmentosa in late infancy, childhood or adulthood. The severe cellular and organ dysfunction of PMM2-CDG typically leads to death in early childhood.

There are currently no FDA approved treatments specific to PMM2-CDG for more than 1000 patients worldwide. Supportive care is aimed at treating symptoms and sequelae.

Glycomine is working on the development of mannose-1-phosphate replacement therapy intended to bypass the genetic block in the pathway and provide continuous exposure over long periods of time. It is expected that such treatment will supply mannose-1-phosphate into affected cells, which will incorporate it into N-glycans of glycoproteins and potentially restore fundamental bodily functions and improve quality of life for both patients and their families.

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