Article CAS PubMed Central PubMed Google Scholar Moses, S. Despite gross glycogenn, the Electrolyte balance benefits may be largely asymptomatic without hypoglycemia. Ai JHe W, Huang X, Wu Y, Lei Y, Yu C, Görgülü K, Diakopoulos KN, Lu N, Zhu Y.

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Glycogen Storage Disorders -Center for Rare Disease Therapy -UPMC Children's Hospital of Pittsburgh Stotage storage diseases Energy drinks for immune system encompass glycogeb group of rare Reseaech diseases due dysfunction of glycogen metabolism. Hypoglycemia is Diabetes complications coma most Researdh primary manifestation of GSD, and Electrolyte balance benefits Rdsearch glucose metabolism can Sgorage neurological damage. The aims of this study Electrolyte balance benefits to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus.

Research on glycogen storage disease -

Indeed, a metabolic imbalance results in overnight hypoglycemia and ketosis, that are associated to short stature, osteopenia, and neurologic complications [ 43 ]. GSDs types 0, VI and particularly type IX would benefit from a strict glycemia monitoring.

A minority of patients with mutations of PHKA2 and PHKG2 associated to a severe phenotype often require overnight feeding to maintain euglycemia [ 85 ].

Since gluconeogenesis is preserved, protein supplementation provides gluconeogenic precursors that can be used for repletion of Krebs cycle intermediates and endogenous glucose production in GSD types 0, IV, VI and IX. By improving glucose homeostasis, hepatic glycogen accumulation and secondary complications might be restrained.

High protein intake is especially needed in GSD type VI to improve muscle function [ 44 ]. In Ross and co-workers [ 85 ] described the efficacy of an extended-release cornstarch Glycosade in GSD types 0, III, VI and IX to achieve a longer time of euglycemia during the night, with stable values of other markers of metabolic control and hepatic function.

In the United States, the extended-release cornstarch preparation has been approved for nocturnal use in GSD patients above 5 years of age. However, the administration of Glycosade in patient between 2 and 5 years of age resulted safe and effective as well [ 86 ].

Adverse effects such as abdominal distension, diarrhea and flatulence have been reported, but to date they were not recorded in patients with GSD types 0, VI and IX [ 61 ].

Patients with GSD type 0 are treated with frequent feeds of hyperglucidic diet plus cornstarch and protein supplementation. Patients with GSD type IV are managed with hyperglucidic diet plus cornstarch, nocturnal enteral feeding, protein enrichment with the aim to limit the accumulation of glycogen, to prevent catabolism and to improve growth and fasting tolerance.

The more severe forms are treated with liver transplantation [ 26 ]. For GSD type XI, Pennisi and co-workers [ 63 ] proposed the nocturnal enteral nutrition in younger children and in patients with a severe growth delay in order to prevent fasting hypoglycemia.

Frequent, small meals, restricted in glucose and galactose, and raw cornstarch administration at night are used to prevent metabolic acidosis, which may occur at times of surgery or other stresses.

Hypercholesterolemia may require a medical treatment with statins after five years of age; bicarbonate supplementation may be required to balance the urinary bicarbonate loss [ 63 ]. According to the available data, universally accepted guidelines for the management of these types of GSDs have not been defined.

Nevertheless, an appropriate follow-up should be provided, in order to establish a good metabolic control and monitor the possible complications. Medical and nutritional evaluations and blood assessment, including complete liver and renal function, lipid profile, calcium-phosphate metabolism, serum electrolytes, blood gas analysis and urinalysis, should be fulfilled every 6 months on average; a higher frequency is recommended in younger patients and in those who have not achieved a metabolic balance.

A continuous glucose monitoring may be helpful to survey the glycemic fluctuations, especially in younger patients. Alpha-fetoprotein levels along with abdomen ultrasound can be used to screen for hepatocellular carcinoma, even though there are no validated surveillance protocols to date [ 37 ].

GSD type IV patients require a complete cardiac function evaluation, including electrocardiogram and echocardiography.

For patients with GSD types VI and IX after 5 years of age a cardiac evaluation is recommended every 1—2 years [ 44 ]. Regarding the bone metabolism, a careful assessment of calcium and vitamin D intake and monitoring of OH vitamin D level is recommended.

Calcium, phosphate and vitamin D supplementations, along with annual DXA scan evaluation, are required to prevent osteopenia and fractures, particularly in GSD type XI, along with a surveillance of renal function [ 61 ].

Skeletal X-Rays are required in GSD type XI to evaluate rickets evolution [ 55 , 56 ]. GSDs type 0, IV, VI, IX and XI with liver involvement may have a similar clinical presentation.

However, these diseases exhibit a phenotypic continuum, and even in the mildest forms, regular monitoring and dietary adjustments are necessary to restrain disease progression and complications. Some cases may exhibit a clinical burden with severe organ complications.

Building a proper knowledge among physicians about these rare conditions is crucial to improve prognosis and quality of life of patients, especially those affected by the most severe forms.

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JM conceptualized the research, gathered and analyzed the data, and wrote the initial manuscript. DV helped with the data analyses and draft of the initial manuscript. BT reviewed the neuroimaging scans. MC coordinated the study, and revised and conducted critical reviews of the manuscript for key intellectual content.

MS helped with the data analyses. All authors contributed to the article and approved the submitted version. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior-Brazil CAPES conferred to JM and DV Finance Code The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The authors are grateful to the families and children who participated in the study. Kanungo S, Wells K, Tribett T, El-Gharbawy A. Glycogen Metabolism and Glycogen Storage Disorders.

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Hum Mol Genet — De Angelis LC, Brigati G, Polleri G, Malova M, Parodi A, Minghetti D, et al. GSD9c results from impaired gamma unit of phosphorylase kinase enzyme function in liver and testis, with early childhood presentations of recurrent hypoglycemia, hepatomegaly progressing to liver cirrhosis and end stage liver disease; apart from motor delay, hepatosplenomegaly, renal tubular damage and muscle weakness Because the gamma subunit contains the catalytic site of the enzyme, GSD9C typically has a more severe phenotype.

In personal experience SK unpublished data , a teenager presented with seizure disorder, microcephaly, intellectual disability, short stature apart from clinical presentations noted above. Apart from clinical presentation noted above, elevated liver enzymes and lactate with severe fasting ketosis in setting of normal triglycerides creatine kinase CK and uric acid can be seen.

Measurement of enzyme activity in liver may help but diagnostic confirmation includes molecular analysis of PHKG2 gene Nutritional approaches to prevent recurrent hypoglycemia with high-protein and complex carbohydrates and symptomatic treatment and management for any hypoglycemia related complications may be helpful.

In personal experience SK unpublished data , teenage presentation of a GSD9c case with liver failure was treated successfully with liver transplantation and at 3-year post transplantation, showed improvement in cognitive abilities in late adolescence, to secure successful vocational training and employment, improved muscle strength, resolution of hepatosplenomegaly and seizures.

GSD9C is an autosomal recessive disorder caused by mutations of the PHKG2 gene which encodes the gamma subunit of phosphorylase kinase on chromosome 16p GSD3, also known as Cori Disease or Forbes disease results from glycogen debrancher enzyme GDE deficiency with impaired glycogen breakdown and abnormal glycogen accumulation, affecting liver, skeletal and cardiac muscles 35 , Muscular symptoms become apparent during and after adolescence though hypertrophic cardiomyopathy seen in younger childhood 43 , As noted above, characteristic findings include fasting hypoglycemia with ketosis, hyperlipidemia, elevated CK, an inverse relationship between a patients age and liver enzymes, lack of lactic acidosis and hyperuricemia 35 , 43 - A diagnosis can be made by mutation analysis of the AGL gene 46 or liver biopsy to detect the enzymatic defect.

Best approaches are nutritional with frequent meals, with high protein content and lesser amounts of UCCS than in GSD1 , or bedtime glycosade helps growth during adolescence Though there are suggestions that a modified Atkins diet improves myopathy symptoms GSD3 has autosomal recessive inheritance, with 58 different reported mutations in the AGL gene on chromosome 1p GSD4, also known as Andersen disease or Brancher deficiency, is a glycogenolysis defect with impaired and few α-1,6-glycosidic bonds along glycogen chain, resulting in abnormal glycogen with limited branch points limited dextran similar to amylopectin or polyglucosan Clinical presentation is variable and historically classified as two hepatic and four neuromuscular forms based upon age of onset and severity More recent studies suggest that GSD4 phenotypes should be considered a continuum of disease as opposed to discreet subtypes 49 , The classical hepatic GSD4 typically presents within 18 months of birth with patients having a failure to thrive, hepatosplenomegaly, and liver cirrhosis As the disease progresses, liver failure ultimately results, leading to death by the age of 5 unless a liver transplant is performed A non-progressive hepatic form with a similar presentation has also been described 52 , Neuromuscular variants range in onset from in utero presenting perinatally as fetal akinesia deformation sequence FADS to adulthood as adult polyglucosan body disease APBD with wide severity range from perinatal death to mild symptoms Commonly seen features of the neuromuscular variant of disease includes: hypotonia, muscle atrophy, myopathy, cardiomyopathy, central nervous system CNS , and peripheral nerve system PNS dysfunction Liver dysfunction with abnormal coagulation can be non-specific findings and amylopectin like material deposition can be seen in liver, heart, muscle, brain, spinal cord or reduced glycogen branching enzyme GBE activity seen in liver, muscle or leukocyte; but confirmation made by molecular analysis of GBE1 gene Unlike other liver GSDs, GSD4 has no specific treatment.

Early liver transplant is indicated in patients with the classical hepatic form but only in absence of cardiac or CNS disease GSD4 is rare and has autosomal recessive inheritance with mutations in the GBE1 gene on chromosome 3p GSD9B, also known as phosphorylase kinase deficiency of liver and muscle, have predominant hepatomegaly, short stature seen in early childhood and, sometimes in addition, muscle weakness and hypotonia Can be asymptomatic, but hypoglycemia and reduced enzyme activity can be seen.

Diagnosis is mainly confirmed by mutation analysis of the PHKB gene. Symptomatic with prevention of hypoglycemia with hi-protein and complex carbohydrate diet; though there is no specific treatment for muscle disease GSD9B is an autosomal recessive disorder caused by mutations of β subunit of PHKB gene on chromosome 16q GSD0b, also known as muscle glycogen synthase deficiency, is rare and seems to affect muscle mitochondrial structure and function apart from depleted glycogen Known symptoms include muscle fatigue, exercise intolerance, recurrent exertional syncope, hypertrophic cardiomyopathy, sudden cardiac death without cardiomyopathy 55 - Clinical suspicion with molecular analysis of GYS1 gene provides diagnostic confirmation.

Muscle biopsy can show depleted glycogen; oxidative fibers and abnormal mitochondria 55 - No specific treatment, preventive measures, supportive therapy with high protein complex carbohydrates diet may help. GSD0b is an autosomal recessive disorder caused by mutations of GSY1 gene on chromosome 19q GSD2, also known as Pompe disease or acid maltase deficiency results from impaired lysosomal acid-α-glucosidase GAA function and accumulation of lysosomal glycogen in skeletal, respiratory and cardiac muscle and often considered as lysosomal storage disorder LSD than GSD.

A non-classical infantile form shows slower symptom progression, is less severe with no cardiomyopathy Late-onset Pompe disease childhood, juvenile, and adult forms is often used to describe patients who present after the first year of life with muscle weakness, and hypotonia Clinical suspicion as noted above with characteristic evidence of hypertrophic cardiomyopathy with EKG findings of shortened PR interval and high QRS complexes and elevated CK is seen in the infantile-onset form.

While, proximal myopathy with diaphragmatic weakness is seen in late-onset disease. Elevated blood aminotransferases and CK are common but diagnostic confirmation noted with deficient GAA enzyme activity in lymphocytes, fibroblasts, and muscle or molecular analysis of biallelic GAA gene GAA activity is usually absent in infantile-onset disease or decreased in late-onset disease.

Some genotype—phenotype correlations exist and determined by the type of the mutation 62 , Dried blood spot testing measuring GAA enzyme activity has helped GSD2 to be included in Newborn Screening Evaluation of the CRIM status is important, since CRIM negative status is associated with poor response to ERT and poor prognosis, if immunomodulation is not started early Results of newborn screening in Taiwan demonstrated significant long-term benefits from the early identification and treatment of patients with infantile Pompe disease before symptoms appeared making an argument for its inclusion in newborn screening panels in many states in the U.

and trialed in several countries 65 , Enzyme replacement therapy ERT using human recombinant acid α-glucosidase, the only approved treatment in the US and Europe since , is based on its ability to degrade accumulated lysosomal glycogen and improve cardiac and skeletal muscle function Though, a negative cross reacting immune material CRIM -negative status has high anti-rhGAA IgG antibodies development and resultant reduced ERT therapeutic effect with poor outcomes if not treated early with immunosuppression 65 , If early diagnosis of late-onset disease is made via newborn screening, the question of when to start treatment in an asymptomatic patient is debated.

Improvement in pulmonary function is seen in symptomatic patients with late-onset disease GSD2 is a pan-ethnic autosomal recessive disorder caused by mutations of the GAA gene on chromosome 17q The increasing list of GAA gene pathogenic mutations can be found at www.

The estimated prevalence is considered to be 1 in 5, GSD5, also known as McArdle disease results from deficient muscle phosphorylase activity and results in impaired glycogenolysis leading to exercise intolerance, muscle weakness and cramping alleviated by rest, and exercise induced rhabdomyolysis.

A common history of childhood onset exercise intolerance and a wide range of severity and age of onset reported with most serious complication being renal failure from myoglobinuria and rhabdomyolysis. Apart from clinical suspicion, elevated CK, myoglobinuria and renal dysfunction as common biochemical markers with additional non-invasive diagnostic confirmation with molecular analysis of PYGM gene is indicated.

Invasive muscle biopsy with negative muscle phosphorylase activity can help diagnosis too. Oral sucrose loading 30—40 minutes before exercise helps exercise tolerance as exogenous fuel source to help energy gap with lack of endogenous glucose from glycogenolysis and free fatty acids availability until ~10 minutes into exercising Regular exercise of moderate intensity helps maximize circulatory capacity and increase fuel delivery to muscles GSD5 is an autosomal recessive disorder caused by mutations of PYGM gene on chromosome 11q GSD7, also known as Tarui disease results from deficient muscle subunit of phosphofructokinase PFK enzyme as a rate limiting factor, with resultant impaired glycogenolysis and glycolysis.

The classical form is characterized by exercise intolerance, often with rhabdomyolysis , muscle cramps and pain. In some cases jaundice accompanied by increased serum bilirubin, exercise related elevated CK levels, myoglobinuria and myogenic hyperuricemia may also be seen 72 ,

Depending Electrolyte balance benefits the type of GSD a glycohen has, glycogen may build up in the liver, Successful weight loss the diseass, or both. GSD can eRsearch affect blood Appetite control planner, the Research on glycogen storage disease, kidneys, and other organs. Normally, glycogen is stored in the liver until the body needs energy. Then, enzymes convert glycogen into glucose so that it can travel through the bloodstream to cells that need fuel. Every cell in the body contains enzymes, but children with GSD lack one of the enzymes responsible for making glycogen or converting glycogen to glucose. GSD is a rare condition.