Abnormal N-glycan fucosylation, galactosylation, and sialylation of IgG in adults with classical galactosemia, influence of dietary galactose intake

Background: Classical galactosemia (CG) (OMIM #230400) is a rare disorder of carbohydrate metabolism, due to deficiency of galactose-1-phosphate uridyltransferase (EC 2.7.7.12). The pathophysiology of the long-term complications, mainly cognitive, neurological, and female infertility remains poorly understood. Objectives: This study investigated (a) the association between specific IgG N-glycosylation biomarkers (glycan peaks and grouped traits) and CG patients (n = 95) identified from the GalNet Network, using hydrophilic interaction ultraperformance liquid chromatography and (b) a further analysis of a GALT c.563A-G/p.Gln188Arg homozygous cohort (n = 49) with correlation with glycan features with patient Full Scale Intelligence Quotient (FSIQ), and (c) with galactose intake. Results: A very significant decrease in galactosylation and sialylation and an increase in core fucosylation was noted in CG patients vs controls (P < .005). Bisected glycans were decreased in the severe GALT c.563A-G/p.Gln188Arg homozygous cohort (n = 49) (P < .05). Logistic regression models incorporating IgG glycan traits distinguished CG patients from controls. Incremental dietary galactose intake correlated positively with FSIQ for the p.Gln188Arg homozygous CG cohort (P < .005) for a dietary galactose intake of 500 to 1000 mg/d. Significant improvements in profiles with increased galactose intake were noted for monosialylated, monogalactosylated, and monoantennary glycans. Conclusion: These results suggest that N-glycosylation abnormalities persist in CG patients on dietary galactose restriction which may be modifiable to a degree by dietary galactose intake

Exploring needs and gaps in psychological supports for people living with rare diseases: A scoping review protocol.

Background A rare disease (RD) is defined in the European Union (EU) as a disease that affects no greater than 5 per 10,000 people (European Commission, 2000). More than 6,000 rare diseases have been identified to date affecting approximately 30 million people in Europe and 400,000 people in Ireland, representing a major public health issue. Living with, and caring for someone with rare disease can have a significant impact on the psychological wellbeing of individuals and families. There is a current dearth of research accessing the experience of people living with a rare disease of accessing various types of psychological support, and assessing needs for such support within the rare disease journey of people living with rare diseases and their caregivers This scoping review aims to examine the existing literature on different types of support, when and how they are used, and to highlight gaps in provision. Methods This scoping review will follow the PRISMA-ScR and Joanna Briggs Institute guidelines and follow the six-stage methodology for scoping reviews: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, (5) collating, summarising and reporting results and (6) knowledge user consultation. Key inclusion criteria have been developed according to the Population Context (PC) framework. The databases OVID MEDLINE, Psycinfo, and CINAHL will be searched for possible relevant articles. Two independent reviewers (EOM AND DN) will screen titles and abstracts of potential articles using a dual review process to ensure all relevant studies are included. Conclusions This scoping review will map the current literature on studies relating to psychological supports for individual and families living with rare disease. It will seek to understand what supports are needed, what supports exists and how services could be improved. This evidence will inform the introduction and the discussion in relation to the wider study on psychological supports