Skeletal and cardiac muscle involvement in children with glycogen storage disease type III

Mogahed, Engy A.; Girgis, Marian; Sobhy, Rodina; Elhabashy, Hala; Abdelaziz, Osama; El‐Karaksy, Hanaa

doi:10.1007/s00431-015-2546-0

Cited by 29 publications

(47 citation statements)

References 11 publications

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“…The prevalence of cardiac involvement in GSD IIIa varies in the literature from 31 to 95% [3,16]. Mogahed et al [21] have found cardiac incidence in GSD IIIa patients to be low and independent from neuromuscular involvement, similar to our patient group, where 2 out of 6 had cardiomyopathy with variable CK levels. Rossi et al [5] and many other authors have shown the cardiac pathology of GSD IIIa to benefit from high-fat diet [5,18,19].…”

Section: Discussionsupporting

confidence: 84%

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

et al. 2020

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Introduction: Glycogen storage disease Type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme, encoded by the AGL gene. Two clinical types of the disease are most prevalent: GSD IIIa involves the liver and muscle, whereas IIIb affects only the liver. The classical dietetic management of GSD IIIa involves prevention of fasting, frequent feeds with high complex carbohydrates in small children, and a low-carb-high-protein diet in older children and adults. Recently, diets containing high amount of fat, including ketogenic and modified Atkins diet (MAD), have been suggested to have favorable outcome in GSD IIIa. Methods: Six patients, aged 3–31 years, with GSD IIIa received MAD for a duration of 3–7 months. Serum glucose, transaminases, creatine kinase (CK) levels, capillary ketone levels, and cardiac parameters were followed-up. Results: In all patients, transaminase levels dropped in response to MAD. Decrease in CK levels were detected in 5 out of 6 patients. Hypoglycemia was evident in 2 patients but was resolved by adding uncooked cornstarch to diet. Conclusion: Our study demonstrates that GSD IIIa may benefit from MAD both clinically and biochemically.

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Section: Discussionsupporting

confidence: 84%

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

et al. 2020

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“…Nevertheless, it has the potential to complement a gene therapy approach by ameliorating the cellular abnormalities associated with specific GSDs. In addition to liver complications, a high percentage of GSD III patients also eventually develop muscle weakness or heart complications 37, 38, 39. As expected, GYS2-1 treatment does not reduce glycogen accumulation in skeletal muscle due to the liver specificity of the GalNAc conjugation delivery approach (Figure S14).…”

Section: Discussionsupporting

confidence: 55%

Inhibition of Glycogen Synthase II with RNAi Prevents Liver Injury in Mouse Models of Glycogen Storage Diseases

et al. 2018

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Glycogen storage diseases (GSDs) of the liver are devastating disorders presenting with fasting hypoglycemia as well as hepatic glycogen and lipid accumulation, which could lead to long-term liver damage. Diet control is frequently utilized to manage the potentially dangerous hypoglycemia, but there is currently no effective pharmacological treatment for preventing hepatomegaly and concurrent liver metabolic abnormalities, which could lead to fibrosis, cirrhosis, and hepatocellular adenoma or carcinoma. In this study, we demonstrate that inhibition of glycogen synthesis using an RNAi approach to silence hepatic Gys2 expression effectively prevents glycogen synthesis, glycogen accumulation, hepatomegaly, fibrosis, and nodule development in a mouse model of GSD III. Mechanistically, reduction of accumulated abnormally structured glycogen prevents proliferation of hepatocytes and activation of myofibroblasts as well as infiltration of mononuclear cells. Additionally, we show that silencing Gys2 expression reduces hepatic steatosis in a mouse model of GSD type Ia, where we hypothesize that the reduction of glycogen also reduces the production of excess glucose-6-phosphate and its subsequent diversion to lipid synthesis. Our results support therapeutic silencing of GYS2 expression to prevent glycogen and lipid accumulation, which mediate initial signals that subsequently trigger cascades of long-term liver injury in GSDs.

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“…CI in glycogen storage disease type-III may manifest as myocardial thickening or hCMP in most patients. 155) 156) Other cardiac manifestations include myocardial fibrosis, dCMP, or heart failure. 157) A single patient with premature coronary artery disease has been described in the literature.…”

Section: Resultsmentioning

confidence: 99%

Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Finsterer

Stöllberger

2016

Korean Circ J

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Little is known regarding cardiac involvement (CI) by neuromuscular disorders (NMDs). The purpose of this review is to summarise and discuss the major findings concerning the types, frequency, and severity of cardiac disorders in NMDs as well as their diagnosis, treatment, and overall outcome. CI in NMDs is characterized by pathologic involvement of the myocardium or cardiac conduction system. Less commonly, additional critical anatomic structures, such as the valves, coronary arteries, endocardium, pericardium, and even the aortic root may be involved. Involvement of the myocardium manifests most frequently as hypertrophic or dilated cardiomyopathy and less frequently as restrictive cardiomyopathy, non-compaction, arrhythmogenic right-ventricular dysplasia, or Takotsubo-syndrome. Cardiac conduction defects and supraventricular and ventricular arrhythmias are common cardiac manifestations of NMDs. Arrhythmias may evolve into life-threatening ventricular tachycardias, asystole, or even sudden cardiac death. CI is common and carries great prognostic significance on the outcome of dystrophinopathies, laminopathies, desminopathies, nemaline myopathy, myotonias, metabolic myopathies, Danon disease, and Barth-syndrome. The diagnosis and treatment of CI in NMDs follows established guidelines for the management of cardiac disease, but cardiotoxic medications should be avoided. CI in NMDs is relatively common and requires complete work-up following the establishment of a neurological diagnosis. Appropriate cardiac treatment significantly improves the overall long-term outcome of NMDs.

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Skeletal and cardiac muscle involvement in children with glycogen storage disease type III

Cited by 29 publications

References 11 publications

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

Inhibition of Glycogen Synthase II with RNAi Prevents Liver Injury in Mouse Models of Glycogen Storage Diseases

Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

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