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

• Published in: Orphanet journal of rare diseases Vol. 16; no. 1; p. 102
• Main Authors: Witters, Peter, Edmondson, Andrew C, Lam, Christina, Johnsen, Christin, Patterson, Marc C, Raymond, Kimiyo M, He, Miao, Freeze, Hudson H, Morava, Eva
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.02.2021; BioMed Central; BMC
• Subjects: Age; Biomarker; Biomarkers; Carbohydrates; Clinical outcomes; Clinical trials; Congenital disorders of glycosylation; Congenital Disorders of Glycosylation - drug therapy; Congenital Disorders of Glycosylation - genetics; Consortia; Dietary supplements; Disease; Glycosylation; Health aspects; Humans; Letter to the Editor; Mannose; Medical research; Natural history; Natural history study; Patients; Phosphomannomutase; Phosphomannomutase 2; Phosphotransferases (Phosphomutases) - deficiency; Phosphotransferases (Phosphomutases) - genetics; PMM2-CDG; Professionals; Prospective Studies; Proteins; Rare diseases; Regression (Disease); Reproducibility of Results; Transferrin; Transferrin - analogs & derivatives; Transferrins; Belgium; United States > US; Natural history study; Biomarker; PMM2-CDG; Transferrin; Congenital disorders of glycosylation; Phosphomannomutase 2
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-021-01751-2

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.