Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)

Abstract

Background PMM2-CDG (CDG-Ia) is the most frequent N-glycosylation disorder. While supplying mannose to PMM2-deficient fibroblasts corrects the altered N-glycosylation in vitro, short term therapeutic approaches with mannose supplementation in PMM2-CDG patients have been unsuccessful. Mannose found no further mention in the design of a potential therapy for PMM2-CDG in the past years, as it applies as ineffective. This retrospective study analyzes the first long term mannose supplementation in 20 PMM2-CDG patients. Mannose was given at a total of 1-2 g mannose/kg b.w./d divided into 5 single doses over a mean time of 60,7 months. Protein glycosylation, blood mannose concentration and clinical presentation were monitored in everyday clinical practice. Results After a mean time period of more than 1 year the majority of patients showed significant improvements in protein glycosylation. Conclusion Long-term dietary D-mannose supplementation shows biological effects in PMM2-CDG, an inherited disorder of mannose metabolism. It improves glycosylation in the majority of patients and could become the first cornerstone in the treatment of this disease.