Nutritional Therapies in Congenital Disorders of Glycosylation (CDG)

Witters, Peter; Cassiman, David; Morava, Éva

doi:10.3390/nu9111222

Cited by 42 publications

(49 citation statements)

References 44 publications

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“…The pathological condition in the heterozygous animals was also reflected in the abnormal glycosylation studies of the serum transferrin and skin fibroblasts harvested from heterozygous animals. In both cases, mass spectrometry showed increased levels of truncated glycans with decreased galactosylation (Figures and S2), which is one of the characteristic features in human PGM1‐CDG patients carrying biallelic mutations . Therefore, our heterozygous mouse model mirrors an important aspect of the human phenotype.…”

Section: Discussionmentioning

confidence: 87%

“…In both cases, mass spectrometry showed increased levels of truncated glycans with decreased galactosylation (Figures 5 and S2), which is one of the characteristic features in human PGM1-CDG patients carrying biallelic mutations. 13,26 Therefore, our heterozygous mouse model mirrors an important aspect of the human phenotype. These heterozygous mice also showed loss of serum glycans, which is the other diagnostic feature of PGM1-deficient patients.…”

Section: Discussionmentioning

confidence: 99%

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A novel phosphoglucomutase‐deficient mouse model reveals aberrant glycosylation and early embryonic lethality

Balakrishnan

Verheijen

Lupo

et al. 2019

J of Inher Metab Disea

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Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes. Midline cleft defects are present at birth. Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early‐onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation. To delineate the pathophysiology of the tissue‐specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)‐knockout (KO) mouse model using CRISPR‐Cas9 technology. After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E‐06), suggesting an embryonic lethality phenotype in the homozygotes. Ultrasound studies of the course of pregnancy confirmed Pgm2‐deficient pups succumb before E9.5. Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality. Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content. However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/− animals, similar to that seen in PGM1‐CDG.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

A novel phosphoglucomutase‐deficient mouse model reveals aberrant glycosylation and early embryonic lethality

Balakrishnan

Verheijen

Lupo

et al. 2019

J of Inher Metab Disea

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“…PUFAs have recently been described to have modulatory effects on voltage-gated ion channels (transmembrane proteins essential for heart and brain function), and thus, a potential anti-epileptic effect [ 218 ]. One should keep in mind that a ketogenic diet may aggravate/potentiate hypoglycemia in these patients [ 15 ].…”

Section: Dietary Supplementation Therapiesmentioning

confidence: 99%

“…Several in vitro and in vivo disease models have been generated allowing the identification of important disease hallmarks, such as novel biomarkers and the screening and testing of possible therapeutic approaches. As a result, advances in treatment options have been made for some CDG [ 14 , 15 , 16 ] but the majority of CDG still remain without effective treatment.…”

Section: Introductionmentioning

confidence: 99%

CDG Therapies: From Bench to Bedside

Brasil

Pascoal

Francisco

et al. 2018

IJMS

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Congenital disorders of glycosylation (CDG) are a group of genetic disorders that affect protein and lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 100 different disorders have been reported and the number is rapidly increasing. Since glycosylation is an essential post-translational process, patients present a large range of symptoms and variable phenotypes, from very mild to extremely severe. Only for few CDG, potentially curative therapies are being used, including dietary supplementation (e.g., galactose for PGM1-CDG, fucose for SLC35C1-CDG, Mn2+ for TMEM165-CDG or mannose for MPI-CDG) and organ transplantation (e.g., liver for MPI-CDG and heart for DOLK-CDG). However, for the majority of patients, only symptomatic and preventive treatments are in use. This constitutes a burden for patients, care-givers and ultimately the healthcare system. Innovative diagnostic approaches, in vitro and in vivo models and novel biomarkers have been developed that can lead to novel therapeutic avenues aiming to ameliorate the patients’ symptoms and lives. This review summarizes the advances in therapeutic approaches for CDG.

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“…The mechanism is still poorly understood, although in CDG-Ib, alimentary addition of mannose appear to bypass the defective step (conversion of fructose-6-phosphate to mannose-6-phosphate) by allowing for the formation of mannose-6-phosphate via the action of hexokinase [ 15 ]. In their article, Morava and her group presented an accurate overview of very recent data on the contributions of nutritional therapy by evaluating many of the different options for nutritional therapy that have somehow been associated with a positive effect on liver function in CDG [ 16 ]. The questions these authors, however, pose include whether or not these dietary interventions are sufficient and whether these dietary interventions are the most efficient therapies for CDG.…”

Section: Hepatopathies Due To Inherited Metabolic/genetic Defectsmentioning

confidence: 99%

Nutrition and Liver Disease

2017

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Malnutrition in children and adults with advanced liver disease represents a tremendous challenge as the nutritional problems are multifactorial. This Editorial comments the articles appearing in this special issue of Nutrients, “Nutrition and Liver disease” dealing with multiple diagnostic and therapeutic features that relate the outcomes of liver disease to nutrition. To improve quality of life and prevent nutrition-related medical complications, patients diagnosed with advanced liver disease should have their nutritional status promptly assessed and be supported by appropriate dietary interventions. Furthermore specific food supplements and/or restriction diets are often necessary for those with hepatic conditions associated with an underlying metabolic or nutritional or intestinal disease.

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Nutritional Therapies in Congenital Disorders of Glycosylation (CDG)

Cited by 42 publications

References 44 publications

A novel phosphoglucomutase‐deficient mouse model reveals aberrant glycosylation and early embryonic lethality

A novel phosphoglucomutase‐deficient mouse model reveals aberrant glycosylation and early embryonic lethality

CDG Therapies: From Bench to Bedside

Nutrition and Liver Disease

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