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Table 1 Studies on therapy and PMM2-CDG disease modeling with intervention

From: Unsuccessful intravenous D-mannose treatment in PMM2-CDG

Description Subject Mutation Outcome Reference
Continuous infusion of D-mannose (0.8 g/kg/day), for 5 months during the first year of life Human c.422G > A (p.Arg141His) and c.691G > A (p.Val231Met). Unsuccessful This study
Oral acetazolamide dosages from 6.8 to 16.7 mg/kg per day were well tolerated. Treatment lasted 6-months, followed by a randomized 5-week withdrawal phase. Human 24 subjects with various mutations Clinical improvement of cerebellar syndrome Ann Neurol. 2019;85:740–51.
Five children with PMM2-CDG, received enteral supplementation with d-mannose 100 mg/kg every 3 h for 9 d. Humans F119 L/R141H
R141H/unknown
Unsuccessful Acta Paediatr. 1998;87:884–8.
Continuous infusion of mannose 5.7 g/kg/day, for 3 weeks, within first year of life. Stable serum mannose levels up to 2.0 mmol/L were maintained. No signs of liver or renal toxicity. Humans Not reported Unsuccessful Acta Paediatr. 1997;86:1138–40.
Oral doses of 0.17 g
(1.0 mmol) mannose/kg body weight every 3.5 h, for 6 months. Patient was 12 months old at start of treatment.
Human Phe119Leu/ Arg141His Unsuccessful Eur J Pediatr. 1998;157:605–6.
Cultured fibroblasts, 0.25 mmol/L D-mannose added to the culture medium Human fibroblasts Not reported N-linked glycosylation restored to normal J Clin Invest. 1996;97:1478–87.
Cultured fibroblasts, 1 mmol/L D-mannose added to the culture medium Human fibroblasts Not reported Recovery of GDP-Mannose pools Glycobiology. 2000;10:829–35.
Cultured fibroblasts, 1 mmol/L D-mannose added to the culture medium
In addition, glucose reduction from 5 mmol/L to 0.5 mmol/L improved D-mannose uptake and restoral of N-glycosylation
Human fibroblasts Not reported N-linked glycosylation restored to normal Glycoconj J. 1998;15:499–505.
Cultured fibroblasts, 0.25 mmol/L D-mannose added to the culture medium Human fibroblasts Not reported N-linked glycosylation restored to normal Biochem Mol Med. 1997;61:161–7.
Treatment of female mice with 9 mg
mannose per mL drinking water, 1 week before mating
Mice Pmm2 R137H/F118 L embryos Successful Nat Med. 2011;18:71–3.
Treatment of female mice with 9 mg
mannose per mL drinking water, 1 week before mating
Mice Pmm2 F115 L embryos Successful Hum Mol Genet. 2016;25:2182–93.