The first step in glycogenolysis is the release of glucosephosphate GP from glycogen by the action of glycogen phosphorylase. The glucosephosphate released by glycogen phosphorylase is converted to glucosephosphate GP by the action of phosphoglucomutase. It should be noted that muscle lacks glucosephosphatase and therefore does not release glucose into the blood.
GSDs type 1 is the result of genetic disorders in the metabolism of glucosephosphatase [3]. Glucosephosphate is synthesized in the cytoplasm of hepatocytes and must be transported into the lumen of the endoplasmic reticulum ER where it is acted upon by glucosephosphatase yielding glucose which is transported back to the cytoplasm and then through the hepatic GLUT2 transporter into the blood.
Glucosephosphate translocase1 G6PT1 is the transporter protein that provides a GP channel between the cytoplasm and the E. GLUT2 deficiency results in a failure to export glucose, an increased intracellular glucose level and reduced degradation of glycogen: eventually there is increased glycogen storage and hepatomegaly. As mentioned above, glycogen is a branched polymer. While glycogen phosphorylase works well at removing glucose from alpha- 1,4 -linkages, it does not work at branch points.
Lysosomes are subcellular organelles that recycle cellular macromolecules. All LSDs are caused by a missing or nonfunctional lysosomal enzyme.
In the case of GSD 2, this enzyme is lysosomal acid alpha-glucosidase gene name GAA , which breaks down glycogen into glucose for use as a cellular energy source. Mutation in the GAA gene results in the toxic accumulation of glycogen in lysosomes. The overall incidence of GSD all forms in Europe, Canada, and the United States is estimated to be between 1 in 20, and 1 in 40, This incidence is probably an underestimate since some individuals can have a very mild form of GSD that is never diagnosed and other forms can result in fetal or neonatal sudden death and go undiagnosed.
There are frequency differences between ethnic groups, e. GSD type 6 is more common in the old order Mennonite population than the general population. Figure 1 summarizes the pathophysiology for each GSD, along with organ s affected, as well as the potential signs.
In general, GSDs primarily affect the liver, skeletal muscle, or both. An inability to synthesize glycogen e. The inability to properly release glucose from glycogen can result in the abnormal accumulation of glycogen.
In the liver e. In skeletal muscle, e. GSDs are a diverse set of rare inborn errors of carbohydrate metabolism that can have a very variable phenotypic presentation even within the same GSD type. Obtaining a family pedigree is useful in establishing the mode of inheritance. Most GSDs show an autosomal recessive inheritance, but a few, e. In GSD Type 1, glycogenolysis in the liver results in increased lactic acid production lactic acidosis due to the intracellular accumulation of glucosephosphate which stimulates the glycolytic pathway.
The blood tests would include serum glucose, anion gap, serum lactate, pH, serum uric acid, a lipid panel, serum gamma-glutamyltransferase, serum alkaline phosphatase, calcium, phosphorus, urea, and creatinine levels, complete blood count CBC and differential. Urine analysis would include testing for aminoaciduria, proteinuria, and microalbuminuria in older patients as well as excreted uric acid and calcium. Liver and kidney MRI or CT are routinely done for adults and ultrasonography for patients less than 16 years of age.
Key overall goals are to treat or avoid hypoglycemia, hyperlactatemia, hyperuricemia, and hyperlipidemia. Hypoglycemia is avoided by consuming starch and an optimal, physically modified form is now commercially available. Hyperuricemia is treated with allopurinol and hyperlipidemia with statins. GSD type 2 can now be treated with enzyme replacement therapy ERT , using recombinant alglucosidase alfa which degrades lysosomal glycogen [6]. Liver transplantation should be considered for patients with GSD type 4 classical and progressive hepatic forms and for GSDs that have progressed to hepatic malignancy or failure.
GSDs are not common and should be managed with an interprofessional team including nurses and dietitians. The key overall goals are to treat or avoid hypoglycemia, hyperlactatemia, hyperuricemia, and hyperlipidemia.
These patients need lifelong monitoring and despite optimal treatment, the outcomes are poor. Contributed by William Stone, MD. This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. National Center for Biotechnology Information , U.
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This can create other problems if your child has certain types of GSD such as:. There is no way to prevent glycogen storage disease. But early treatment can help control symptoms once a child has GSD. If you or your partner have GSD, or a family history of this disease, see a genetic counselor before you get pregnant. He or she can find out your chances of having a child with GSD.
A child with GSD may have special needs. Be sure that your child gets regular medical care. Regular medical visits will also help you keep up with new treatment options. Health Home Conditions and Diseases. These types are also known by other names: Type I or von Gierke disease. This is the most common form of GSD. Glycogen builds up in the liver. Symptoms often appear in babies around 3 to 4 months old. They may include low blood sugar hypoglycemia and a swollen belly because of an enlarged liver.
It collects in the liver and in muscle tissues. Symptoms include a swollen belly, delayed growth, and weak muscles. Type IV or Andersen disease. People with type IV form abnormal glycogen. This creates scarring cirrhosis of the liver and other organs such as muscle and the heart. What causes glycogen storage disease in a child? Glycogen storage disease is passed down from parents to children hereditary. Which children are at risk for glycogen storage disease? Glycogen storage disease is passed down from parents to children inherited.
Someone is more at risk for GSD if they have a family member with the disease. What are the symptoms of glycogen storage disease in a child? Because GSD most often affects the muscles and the liver, those areas show the most symptoms.
General symptoms of GSD may include: Not growing fast enough Not feeling comfortable in hot weather heat intolerance Bruising too easily Low blood sugar hypoglycemia An enlarged liver A swollen belly Weak muscles low muscle tone Muscle pain and cramping during exercise Symptoms for babies may include: Too much acid in the blood acidosis High blood cholesterol levels hyperlipidemia The symptoms of GSD may look like other health problems.
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