Hepatic glycogen storage diseases: pathogenesis, clinical symptoms and therapeutic management

Szymańska, Edyta; Jóźwiak-Dzięcielewska, Dominika A.; Gronek, Joanna; Niewczas, Marta; Czarny, Wojciech; Rokicki, Dariusz; Gronek, Piotr

doi:10.5114/aoms.2019.83063

Cited by 9 publications

(11 citation statements)

References 67 publications

(80 reference statements)

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“…High protein intake may contribute to ketosis as well [20]. For GSD III, blood or urinary ketones could be used to assess optimal metabolic control of such cases [18,21]. In the current study, there were no statistically significant differences between cases with LBMD and cases with normal BMD as regards triglycerides, lactates, RBS and compliance to starch therapy (p= 0.4, p= 0.7, p= 0.3, p= 0.7) respectively.…”

Section: P R E P R I N Tmentioning

confidence: 99%

A high prevalence of low bone mineral density in children with glycogen storage disease type III

et al. 2021

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IntroductionGlycogen storage disease III (GSD III) is an inborn error of carbohydrate metabolism that involves mainly the liver and skeletal muscles with rare potential systemic complications as osteoporosis. The aim of work of the current study was to screen children with GSD III for osteoporosis using Dual-emission-X-ray absorptiometry (DXA) scan and to measure associated parathormone (PTH) and vitamin D. Our secondary objective is to correlate between the degree of osteoporosis and the muscle state as well as the metabolic control.Material and methodsThis cross sectional study included 25 GSD III pediatric cases. The liver biochemical profile, creatine kinase (CK), vitamin D2, PTH levels were tested in addition to electromyogram (EMG), echocardiography and DXA. Twenty-five age and sex matched normal healthy controls were subjected to vitamin D2 analysis and compared to cases.ResultsThe mean ±SD age of the patients was 10.52 ± 3.1 years ranging between 5-18 years. Twenty-one patients (84%) had elevated CK levels, 14 patients (56%) had myopathy and three (12%) had sensory polyneuropathy and almost half of the patients had a mild degree of cardiac muscle hypertrophy. Ten patients (40%) had elevated PTH levels. Twenty-one patients (84%) and 96% of the controls had vitamin D2 deficiency. Thirteen patients (52%) had low BMD; two of them had osteoporosis. Patients with high CK levels significantly had low BMD (P= 0.04).ConclusionsPediatric GSD III patients have a significant prevalence of developing low BMD. It is strongly associated with myopathic changes but not significantly related to metabolic control.

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Section: P R E P R I N Tmentioning

confidence: 99%

A high prevalence of low bone mineral density in children with glycogen storage disease type III

et al. 2021

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“…The overall estimated GSD incidence is 1 case per 10,000 live births ( Beyzaei et al, 2020 ). Like most metabolic diseases, the vast majority of GSDs are inherited in an autosomal recessive (AR) pattern, except for X-linked type IXα ( Brown et al, 2015 ; Szymanska et al, 2021 ). In GSD Ⅱ, the symptoms are caused by mutations in GAA gene and in GSD III, AGL gene.…”

Section: Introductionmentioning

confidence: 99%

“…The clinical manifestations of GSDs range from almost no symptoms to severe cardiac dysfunction, respiratory insufficiency, and sudden death ( Molares-Vila et al, 2021 ). GSDs are divided into hepatic, muscle and mixed types according to glycogen accumulation in tissues ( Lu et al, 2016 ; Zhao et al, 2019 ; Eghbali et al, 2020 ; Szymanska et al, 2021 ). The basic clinical symptoms of hepatic GSD are hypoglycemia and hepatomegaly.…”

Section: Introductionmentioning

confidence: 99%

“…Liver biopsy is an invasive test to assess liver cell enzyme activity. Gene sequencing and genetic analysis, a technology that can provide precise diagnosis and procreation guidance and are more acceptable to patients, is increasingly used in the diagnosis of genetic diseases, including GSD ( Shen and Shi, 2019 ; Fang et al, 2021 ; Huang et al, 2021 ; Li et al, 2021 ; Szymanska et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

et al. 2022

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Background: Glycogen storage diseases (GSDs) are known as a group of disorders characterized by genetic errors leading to accumulation of glycogen in various tissues. Since different types of GSD can sometimes be clinically indistinguishable, next generation sequencing is becoming a powerful tool for clinical diagnosis.Methods: 12 patients with suspected GSDs and their parents were enrolled in this study. The clinical and laboratory data of the patients were reviewed. Causative gene variants were identified in the patients using whole exome sequencing (WES) and verified by Sanger sequencing.Results: Genetic testing and analysis showed that 7 patients were diagnosed with GSD II (Pompe disease), 2 patients with GSD III, 1 patient with GSD VI, and 2 patients with GSD IXα. A total number of 18 variants were identified in 12 patients including 11 variants in GAA gene, 3 variants in AGL gene, 2 variants in PYGL gene and 2 variants in PHKA2 gene, of which 9 variants were reported and 9 variants were novel. SIFT, Polyphen-2, Mutation Taster, and REVEL predicted the novel variants (except GAA c.1052_1075 + 47del) to be disease-causing. The 3D structures of wild/mutant type GAA protein were predicted indicating that variants p. Trp621Gly, p. Pro541Leu, p. Ser800Ile and p. Gly293Trp might affect the proteins function via destroying hydrogen bonds or conformational constraints. Neither liver size nor laboratory findings allow for a differentiation among GSD III, GSD VI and GSD IXα.Conclusion: Our study expanded the variation spectrum of genes associated with GSDs. WES, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate results for diagnosing and sub-typing GSD and related diseases in clinical setting.

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“…Glycogen is a highly branched polymer of glucose molecules. It is the main storage form of carbohydrate in humans, primarily within liver and muscles [ 1 ]. Its role is to store glucose and make it available as soon as glycaemia gets low.…”

Section: Introductionmentioning

confidence: 99%

Hepatic glycogen storage diseases type 0, VI and IX: description of an italian cohort

Tagliaferri

Massese

Russo

et al. 2022

Orphanet J Rare Dis

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Background Glycogen storage disease (GSD) type 0, VI and IX are inborn errors of metabolism involving hepatic glycogen synthesis and degradation. We performed a characterization of a large Italian cohort of 30 patients with GSD type 0a, VI, IXa, IXb and IXc. A retrospective evaluation of genetical, auxological and endocrinological data, biochemical tests, and nutritional intakes was assessed. Eventual findings of overweight/obesity and insulin-resistance were correlated with diet composition. Results Six GSD-0a, 1 GSD-VI, and 23 GSD-IX patients were enrolled, with an age of presentation from 0 to 72 months (median 14 months). Diagnosis was made at a median age of 30 months, with a median diagnostic delay of 11 months and a median follow-up of 66 months. From first to last visit, patients gained a median height of 0.6 SDS (from − 1.1 to 2.1 SDS) and a median weight of 0.5 SDS (from − 2.5 to 3.3 SDS); mean and minimal glucose values significant improved (p < 0.05). With respect to dietary intakes, protein intake (g/kg) and protein intake (g/kg)/RDA ratio directly correlated with the glucose/insulin ratio (p < 0.05) and inversely correlated with HOMA-IR (Homeostasis model assessment of insulin resistance, p < 0.05), BMI SDS (p < 0.05) and %ibw (ideal body weight percentage, p < 0.01). Conclusion A prompt establishment of specific nutritional therapy allowed to preserve growth, improve glycemic control and prevent liver complication, during childhood. Remarkably, the administration of a high protein diet appeared to have a protective effect against overweight/obesity and insulin-resistance.

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Hepatic glycogen storage diseases: pathogenesis, clinical symptoms and therapeutic management

Cited by 9 publications

References 67 publications

A high prevalence of low bone mineral density in children with glycogen storage disease type III

A high prevalence of low bone mineral density in children with glycogen storage disease type III

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

Hepatic glycogen storage diseases type 0, VI and IX: description of an italian cohort

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