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Randomized Controlled Trial
. 2021 Feb 25;16(1):102.
doi: 10.1186/s13023-021-01751-2.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

Peter Witters #  1   2 , Andrew C Edmondson #  3 , Christina Lam  4   5 , Christin Johnsen  6 , Marc C Patterson  7 , Kimiyo M Raymond  8 , Miao He  9 , Hudson H Freeze #  10 , Eva Morava #  11
Affiliations
Randomized Controlled Trial

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

Peter Witters et al. Orphanet J Rare Dis. .

Abstract

A recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study's conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients' lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

Keywords: Biomarker; Congenital disorders of glycosylation; Natural history study; PMM2-CDG; Phosphomannomutase 2; Transferrin.

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Conflict of interest statement

PW, ACE, CL, CJ, KMR, MH, EM declare that they have no competing interests. HF is a consultant for Cerecor, Inc.

Figures

Fig. 1
Fig. 1
Measurements of transferrin glycosylation by MS. Each circle represents one measurement. Measurements in the same patient over time are connected by thin lines. A Loess regression curve is plotted a black dotted line. The horizontal grey line represents the upper limit of normal. Measurements include a ratio of mono-glycosylated (hypoglycosylated) transferrin to di-glycosylated (normal) transferrin, b ratio of a-glycosylated (non-glycosylated) transferrin to di-glycosylated (normal) transferrin
See this image and copyright information in PMC

Comment in

  • Mannose supplementation in PMM2-CDG.
    Taday R, Park JH, Grüneberg M, DuChesne I, Reunert J, Marquardt T. Taday R, et al. Orphanet J Rare Dis. 2021 Aug 11;16(1):359. doi: 10.1186/s13023-021-01988-x. Orphanet J Rare Dis. 2021. PMID: 34380532 Free PMC article.

References

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