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 to be 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 57,75 ± 25,85 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 Dietary mannose supplementation shows biological effects in PMM2-CDG patients improving glycosylation in the majority of patients. A double-blind randomized study is needed to examine the role of mannose in the design of a therapy for children with PMM2-CDG in more detail.

BackgroundPMM2-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.ResultsAfter a mean time period of more than 1 year the majority of patients showed significant improvements in protein glycosylation.ConclusionLong-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.

In this response to the letter by Witters et al., we refer to the authors' arguments regarding spontaneous enhancement of glycosylation and the claim, that mannose has no place in the treatment of PMM2-CDG. Our paper “Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)” has shown that further investigation of mannose in PMM2-CDG is worthwhile alongside other treatment options and should not be dismissed off-hand without the willingness to prove or disprove it in controlled prospective clinical trials.

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.