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Contains fulltext : 225114.pdf (publisher's version ) (Open Access), Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and current

Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 6 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently

Contains fulltext : 225114.pdf (publisher's version ) (Open Access), Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and current

Item does not contain fulltext, MAN1B1-CDG has recently been characterized as a type II congenital disorder of glycosylation (CDG), disrupting not only protein N-glycosylation but also general Golgi morphology. Using our high-throughput, quantitative ultra-performance liquid chromatography assay, we achieved a detailed characterization of the glycosylation changes in both total serum glycoproteins and isolated serum IgG from ten previously reported MAN1B1-CDG patients. We have identified and quantified novel hybrid high-mannosylated MAN1B1-CDG-specific IgG glycans and found an increase of sialyl Lewis x (sLex) glycans on serum proteins of all patients. This increase in sLex has not been previously reported in any CDG. These findings may provide insight into the pathophysiology of this CDG.

Item does not contain fulltext, MAN1B1-CDG has recently been characterized as a type II congenital disorder of glycosylation (CDG), disrupting not only protein N-glycosylation but also general Golgi morphology. Using our high-throughput, quantitative ultra-performance liquid chromatography assay, we achieved a detailed characterization of the glycosylation changes in both total serum glycoproteins and isolated serum IgG from ten previously reported MAN1B1-CDG patients. We have identified and quantified novel hybrid high-mannosylated MAN1B1-CDG-specific IgG glycans and found an increase of sialyl Lewis x (sLex) glycans on serum proteins of all patients. This increase in sLex has not been previously reported in any CDG. These findings may provide insight into the pathophysiology of this CDG.

Item does not contain fulltext, MAN1B1-CDG has recently been characterized as a type II congenital disorder of glycosylation (CDG), disrupting not only protein N-glycosylation but also general Golgi morphology. Using our high-throughput, quantitative ultra-performance liquid chromatography assay, we achieved a detailed characterization of the glycosylation changes in both total serum glycoproteins and isolated serum IgG from ten previously reported MAN1B1-CDG patients. We have identified and quantified novel hybrid high-mannosylated MAN1B1-CDG-specific IgG glycans and found an increase of sialyl Lewis x (sLex) glycans on serum proteins of all patients. This increase in sLex has not been previously reported in any CDG. These findings may provide insight into the pathophysiology of this CDG.

The Saskatchewan River Delta (SRD) is the largest freshwater inland delta in North America, covering over 950 000 hectares in central Saskatchewan and Manitoba. The wetlands in the SRD provide valuable ecosystem services and support considerable biodiversity. The Opaskwayak Cree Nation (OCN) has expressed concerns regarding the loss of wildlife in the SRD, among other ecological concerns, due to anthropogenic development. Using an ethnoecological approach, the indigenous knowledge of the OCN was documented through an analysis of wetland-based practices. A variety of methods were employed in the research including participant observation, interviews, document review and verification workshops. Interviews held with community Elders also focused on the connections between a life on the land, well-being and cultural identity. The research revealed the need for a more holistic approach to management of the sensitive wetland ecosystems located with OCN traditional territory that reflects the changing values of the community.

The Saskatchewan River Delta (SRD) is the largest freshwater inland delta in North America, covering over 950 000 hectares in central Saskatchewan and Manitoba. The wetlands in the SRD provide valuable ecosystem services and support considerable biodiversity. The Opaskwayak Cree Nation (OCN) has expressed concerns regarding the loss of wildlife in the SRD, among other ecological concerns, due to anthropogenic development. Using an ethnoecological approach, the indigenous knowledge of the OCN was documented through an analysis of wetland-based practices. A variety of methods were employed in the research including participant observation, interviews, document review and verification workshops. Interviews held with community Elders also focused on the connections between a life on the land, well-being and cultural identity. The research revealed the need for a more holistic approach to management of the sensitive wetland ecosystems located with OCN traditional territory that reflects the changing values of the community.

The Saskatchewan River Delta (SRD) is the largest freshwater inland delta in North America, covering over 950 000 hectares in central Saskatchewan and Manitoba. The wetlands in the SRD provide valuable ecosystem services and support considerable biodiversity. The Opaskwayak Cree Nation (OCN) has expressed concerns regarding the loss of wildlife in the SRD, among other ecological concerns, due to anthropogenic development. Using an ethnoecological approach, the indigenous knowledge of the OCN was documented through an analysis of wetland-based practices. A variety of methods were employed in the research including participant observation, interviews, document review and verification workshops. Interviews held with community Elders also focused on the connections between a life on the land, well-being and cultural identity. The research revealed the need for a more holistic approach to management of the sensitive wetland ecosystems located with OCN traditional territory that reflects the changing values of the community.

The Saskatchewan River Delta (SRD) is the largest freshwater inland delta in North America, covering over 950 000 hectares in central Saskatchewan and Manitoba. The wetlands in the SRD provide valuable ecosystem services and support considerable biodiversity. The Opaskwayak Cree Nation (OCN) has expressed concerns regarding the loss of wildlife in the SRD, among other ecological concerns, due to anthropogenic development. Using an ethnoecological approach, the indigenous knowledge of the OCN was documented through an analysis of wetland-based practices. A variety of methods were employed in the research including participant observation, interviews, document review and verification workshops. Interviews held with community Elders also focused on the connections between a life on the land, well-being and cultural identity. The research revealed the need for a more holistic approach to management of the sensitive wetland ecosystems located with OCN traditional territory that reflects the changing values of the community.