PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis

Aggarwal, Varun; Dobrolet, Nancy; Fishberger, Steven B.; Zablah, Jenny E.; Jayakar, Parul; Ammous, Zineb

doi:10.4103/0974-2069.154149

Cited by 20 publications

(14 citation statements)

References 12 publications

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“…For example, cardiac hypertrophy seen in LAMP2, PRKAG2, PTPN11, and RAF1 pathogenic variant carriers can represent a genocopy of hypertrophy seen with sarcomeric pathogenic variants; yet LAMP2, PRKAG2, PTPN11, and RAF1 patients have different clinical courses and management needs. 28,29 In sarcomeric carriers, genotype status is associated with long-term outcomes, including allcause mortality. 30,31 In DCM, there is evidence for prognostication value of genetic testing [32][33][34][35] and management implications for specific genetic findings, such as consideration of implantable cardioverter defibrillator (ICD) for primary prevention in carriers of LMNA pathogenic variants.…”

Section: Methodsmentioning

confidence: 99%

Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Hershberger

Givertz

et al. 2018

Genetics in Medicine

199

162

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Section: Methodsmentioning

confidence: 99%

Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Hershberger

Givertz

et al. 2018

Genetics in Medicine

199

162

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“…The biochemical mechanism underlying the formation of this material remains undefined [41] . Ablation of atrioventricular accessory pathways caused by mutations in the PRKAG2 gene is not usually effective to correct conduction system abnormalities [42] .…”

Section: Glycogen Synthesismentioning

confidence: 99%

Glycogen metabolism in humans

Adeva‐Andany¹,

et al. 2016

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In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5ʹ-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis. Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase. Glycogen branching enzyme introduces branch points in the glycogen particle at even intervals. Laforin and malin are proteins involved in glycogen assembly but their specific function remains elusive in humans. Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points. In the lysosomes, glycogen degradation is catalyzed by α-glucosidase. The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell. Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases.

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“…19,20 Cardiac abnormality manifesting in conduction alterations has been associated with mutations in AMPK regulating gene thus implicating this signalling pathway. 21 From our study, we found that metformin restored doxorubicin reduced RR interval. This phenomenon of reduced RR interval is reflective of slowed heart beat and hence bradycardia.…”

Section: Discussionmentioning

confidence: 77%

Effect of metformin on ECG, HR and BP of rats administered with cardiotoxic agent doxorubicin

Emeka

AlAhmed

2017

Int J Basic Clin Pharmacol

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Background: Cardiovascular complications during drug therapy is worrisome and has been known to increase morbidity and mortality. The aim of this study was to investigate the effect of metformin on BP, HR, and ECG, after subacute administration of doxorubicin in rats.Methods: Laboratory acclimatised animals were divided into 4 experimental groups consisting of group I as the control, given 0.5ml normal saline. Group II, received 3mg/kg doxorubicin on alternate days, while group III was given 300mg/kg metformin. The last group of animals were treated with 300mg/kg metformin, 30 min later, the animals were injected doxorubicin ip. The treatment lasted for 15 days thereafter, ECG, HR and BP were measured with anaesthesia.Results: Result showed that doxorubicin induced ECG changes in terms of increased PR and QT intervals significantly. Whereas, QRS and RR intervals were at same time significantly decreased. Metformin was observed to significantly attenuate these changes. In addition, metformin restored decreases in HR that was caused by doxorubicin in a significant fashion. However, metformin alone produced a decrease in HR compared with control. The observed reduced SBP and DBP produced by doxorubicin were also alleviated by the administration of metformin. There were increases in BP parameters measured in normotensive rats with metformin alone.Conclusions: In conclusion, metformin was found to attenuate doxorubicin-induced alteration in ECG pattern and restored the mechanical and physiological functions of the rat heart. Our data further suggests monitoring of CVS changes such as ECG particularly with drugs known to cause myocardial injury.

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PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis

Cited by 20 publications

References 12 publications

Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Glycogen metabolism in humans

Effect of metformin on ECG, HR and BP of rats administered with cardiotoxic agent doxorubicin

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