Hepatic Glycogen Storage Diseases

Derks, Terry G J; Németh, Antal; Adrian, Katrin; Arnell, Henrik; Roskjær, Ann Bech; Beijer, Eva; Boekhorst, Sebastiaan te; Heidenborg, C.; Landgren, Marcus; Nilsson, Mikael; Papadopoulou, Domniki N.; Ross, Katalin M; Sjoqvist, E.; Stachelhaus-Theimer, Ute; Steuerwald, Ulrike; Törnhage, Carl-Johan; Weinstein, David A.

doi:10.1177/2326409817733009

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…NGS approach has also the potential to diagnose disorders with mild biochemical abnormalities or atypical presentations or even to identify new diseases, changing the epidemiology of many disorders. In this respect, the development of extended collaboration networks for rare diseases is worthy (43).…”

Section: Discussion and Conclusive Remarksmentioning

confidence: 99%

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An Overview of Hypoglycemia in Children Including a Comprehensive Practical Diagnostic Flowchart for Clinical Use

Casertano¹,

Rossi

Fecarotta

et al. 2021

Front. Endocrinol.

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Hypoglycemia is the result of defects/impairment in glucose homeostasis. The main etiological causes are metabolic and/or endocrine and/or other congenital disorders. Despite hypoglycemia is one of the most common emergencies in neonatal age and childhood, no consensus on the definition and diagnostic work-up exists yet. Aims of this review are to present the current age-related definitions of hypoglycemia in neonatal-pediatric age, to offer a concise and practical overview of its main causes and management and to discuss the current diagnostic-therapeutic approaches. Since a systematic and prompt approach to diagnosis and therapy is essential to prevent hypoglycemic brain injury and long-term neurological complications in children, a comprehensive diagnostic flowchart is also proposed.

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Section: Discussion and Conclusive Remarksmentioning

confidence: 99%

“…mcg/dl, GH > 7 ng/ml) Provocation test (leucine loading or exercise testing) may be needed in some patients Modified from Vora et al(43).…”

mentioning

confidence: 99%

An Overview of Hypoglycemia in Children Including a Comprehensive Practical Diagnostic Flowchart for Clinical Use

Casertano¹,

Rossi

Fecarotta

et al. 2021

Front. Endocrinol.

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“…Glycogen storage diseases (GSDs) are a group of carbohydrate metabolism disorders, most of which are inherited in autosomal recessive patterns [1]. There are two sorts of GSDs: those that have to do with liver and hypoglycaemia (hepatic GSDs) and those that are linked to neuromuscular presentation [2,3]. Based on the type of enzyme defect, about 16 types have been discovered and numbered from 0 to 15 [1,4].…”

Section: Introductionmentioning

confidence: 99%

Medium-Chain Triglyceride Oil and Dietary Intervention Improved Body Composition and Metabolic Parameters in Children with Glycogen Storage Disease Type 1 in Jordan: A Clinical Trial

Subih,

Qudah,

Janakat

et al. 2024

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Glycogen storage diseases (GSDs) are a group of carbohydrate metabolism disorders, most of which are inherited in autosomal recessive patterns. GSDs are of two types: those that have to do with liver and hypoglycaemia (hepatic GSDs) and those that are linked to neuromuscular presentation. This study aims to assess the impact of dietary intervention, including medium-chain triglyceride (MCT) oil, on anthropometric measurements, body composition analysis and metabolic parameters among Jordanian children and is expected to be the first in the country. A sample of 38 children with glycogen storage disease type 1 (GSD-1) (median age = 6.4 years) were on a diet that included uncooked cornstarch therapy and a fructose-, sucrose- and lactose-restricted diet. Patients started to take MCT oil along with the prescribed diet after the first body composition test. Patients’ nutritional status was re-evaluated three months later. The study results show that the percentage of patients who suffered from hypoglycaemia at the beginning of the study decreased significantly from 94.7% to 7.9% (p < 0.0001). The serum levels of triglycerides, cholesterol, uric acid and lactate decreased significantly after three months of intervention (100–71.1%, 73.7–21.1%, 97.4–52.6% and 94.7–18.4%, respectively). In contrast, there was no statistical difference in neutrophil count. Regarding clinical parameters, liver span was significantly reduced from (16.01 ± 2.65 cm) to (14.85 ± 2.26 cm) (p < 0.0001). There were significant improvements in growth parameters, including height-for-age and BMI-for-age for children aged ≥2 years (p = 0.034 and p = 0.074, respectively). Significant improvements in skeletal muscle mass and bone mineral content were also noticed at the end of the trial (p ≤ 0.05). In conclusion, medium-chain triglyceride therapy is found to improve biochemical and growth parameters in children with GSD-1 in Jordan.

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“…This is achieved by frequent feeding of uncooked or modified cornstarch (for adults or older children) or gastric drip feeding of glucose (for younger children or infants) (Greene et al 1976 ; Correia et al 2008 ; Shah and O’Dell 2013 ). However, the effectiveness of dietary management on long-term metabolic complications including hepatocellular adenomas and carcinomas (HCAs/HCCs) remains unproven and its long-term therapeutic window has been reported to be narrow (Franco et al 2005 ; Wang et al 2011 ; Calderaro et al 2012 ; Derks et al 2017 ; Steunenberg et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells

et al. 2023

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Glucose-6-phosphatase-α (G6Pase-α) catalyzes the hydrolysis of glucose-6-phosphate to glucose and functions as a key regulator in maintaining blood glucose homeostasis. Deficiency in G6Pase-α causes glycogen storage disease 1a (GSD1a), an inherited disorder characterized by life-threatening hypoglycemia and other long-term complications. We have developed a potential mRNA-based therapy for GSD1a and demonstrated that a human G6Pase-α (hG6Pase-α) variant harboring a single serine (S) to cysteine (C) substitution at the amino acid site 298 (S298C) had > twofold increase in protein expression, resulting in improved in vivo efficacy. Here, we sought to investigate the mechanisms contributing to the increased expression of the S298C variant. Mutagenesis of hG6Pase-α identified distinct protein variants at the 298 amino acid position with substantial reduction in protein expression in cultured cells. Kinetic analysis of expression and subcellular localization in mammalian cells, combined with cell-free in vitro translation assays, revealed that altered protein expression stemmed from differences in cellular protein stability rather than biosynthetic rates. Site-specific mutagenesis studies targeting other cysteines of the hG6Pase-α S298C variant suggest the observed improvements in stability are not due to additional disulfide bond formation. The glycosylation at Asparagine (N)-96 is critical in maintaining enzymatic activity and mutations at position 298 mainly affected glycosylated forms of hG6Pase-α. Finally, proteasome inhibition by lactacystin improved expression levels of unstable hG6Pase-α variants. Taken together, these data uncover a critical role for a single amino acid substitution impacting the stability of G6Pase-α and provide insights into the molecular genetics of GSD1a and protein engineering for therapeutic development.

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Hepatic Glycogen Storage Diseases

Cited by 8 publications

References 13 publications

An Overview of Hypoglycemia in Children Including a Comprehensive Practical Diagnostic Flowchart for Clinical Use

An Overview of Hypoglycemia in Children Including a Comprehensive Practical Diagnostic Flowchart for Clinical Use

Medium-Chain Triglyceride Oil and Dietary Intervention Improved Body Composition and Metabolic Parameters in Children with Glycogen Storage Disease Type 1 in Jordan: A Clinical Trial

Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells

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