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

Peter Witters, Andrew C. Edmondson, Christina Lam, Christin Johnsen, Marc C. Patterson, Kimiyo M. Raymond, Miao He, Hudson H. Freeze, Eva Morava

Research output: Contribution to journalLetterpeer-review

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.

Original languageEnglish (US)
Article number102
JournalOrphanet Journal of Rare Diseases
Volume16
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Biomarker
  • Congenital disorders of glycosylation
  • Natural history study
  • PMM2-CDG
  • Phosphomannomutase 2
  • Transferrin

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study'. Together they form a unique fingerprint.

Cite this