Glycogen storage disease
Encyclopedia
Glycogen storage disease (GSD, also glycogenosis and dextrinosis) is the result of defects in the processing of glycogen
synthesis or breakdown within muscle
s, liver
, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism
(genetically defective enzyme
s) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid
castanospermine
.
Overall, according to a study in British Columbia
, approximately 2.3 children per 100 000 births (1 in 43,000) have some form of glycogen storage disease. In the United States, they are estimated to occur in 1 per 20,000-25,000 births. A Dutch study estimated it to be 1 in 40,000.
deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems.)
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
synthesis or breakdown within muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
s, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism
Inborn error of metabolism
Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others...
(genetically defective enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
castanospermine
Castanospermine
Castanospermine is an indolizine alkaloid first isolated from the seeds of Castanospermum australe. It is a potent inhibitor of some glucosidase enzymes and has antiviral activity....
.
Overall, according to a study in British Columbia
British Columbia
British Columbia is the westernmost of Canada's provinces and is known for its natural beauty, as reflected in its Latin motto, Splendor sine occasu . Its name was chosen by Queen Victoria in 1858...
, approximately 2.3 children per 100 000 births (1 in 43,000) have some form of glycogen storage disease. In the United States, they are estimated to occur in 1 per 20,000-25,000 births. A Dutch study estimated it to be 1 in 40,000.
Types
There are eleven (11) distinct diseases that are commonly considered to be glycogen storage diseases (some previously thought to be distinct have been reclassified). (Although glycogen synthaseGlycogen synthase
Glycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers....
deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems.)
- GSD type VIII: In the past, considered a distinct condition. Now classified with VI. Has been described as X-linked recessiveX-linked recessiveX-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
.
- GSD type X: In the past, considered a distinct condition. Now classified with VI.
| Number | Enzyme deficiency | Eponym | Incidence | Hypo- glycemia Hypoglycemia Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"... ? |
Hepato- megaly Hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass... ? |
Hyperlip- idemia Hyperlipidemia Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood... ? |
Muscle symptoms | Development/ prognosis | Other symptoms >- | GSD type I Glycogen storage disease type I Glycogen storage disease type I or von Gierke's disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase. This deficiency impairs the ability of the liver to produce free glucose from glycogen and from... |
glucose-6-phosphatase | von Gierke's disease | 1 in 50,000- 100,000 births | Yes | Yes | Yes | None | Growth failure | Lactic acidosis Lactic acidosis Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example... , hyperuricemia Hyperuricemia Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:... >- | GSD type II Glycogen storage disease type II Glycogen storage disease type II is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme... |
acid maltase | Pompe's disease | 1 in 60,000- 140,000 births | No | Yes | No | Muscle weakness Muscle weakness Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness... |
*Death by age ~2 years (infantile variant) | >- | glycogen debrancher | Cori's disease or Forbes' disease | 1 in 100,000 births | Yes | Yes | Yes | Myopathy Myopathy In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease... |
>- | glycogen branching enzyme Glycogen branching enzyme A glycogen branching enzyme is an enzyme that takes part in converting glucose to glycogen. It adds branches to the growing glycogen molecule. Glycogen is a branching polymer of large numbers of glucose units linked together. The structure is based on chains of glucose units with linkages between... |
Andersen disease | No | Yes, also cirrhosis Cirrhosis Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function... |
No | None | Failure to thrive Failure to thrive Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine .... , death at age ~5 years |
>- | muscle glycogen phosphorylase | McArdle disease | 1 in 100,000 | No | No | No | Exercise-induced cramps, Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure... |
Renal failure Renal failure Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood... by myoglobinuria Myoglobinuria Myoglobinuria is the presence of myoglobin in the urine, usually associated with rhabdomyolysis or muscle destruction. Myoglobin is present in muscle cells as a reserve of oxygen.-Causes:... >- | GSD type VI Glycogen storage disease type VI Glycogen storage disease type VI is a type of glycogen storage disease caused by a deficiency in liver glycogen phosphorylase or other components of the associated phosphorylase cascade system.It is also known as "Hers' disease", after Henri G... |
liver glycogen phosphorylase | Hers' disease | 1 in 65,000- 85,000 births | Yes | Yes | No | None | >- | muscle phosphofructokinase | Tarui's disease | No | No | No | Exercise-induced muscle cramps and weakness | growth retardation | >- | phosphorylase kinase Phosphorylase kinase Phosphorylase kinase is a serine/threonine-specific protein kinase which activates glycogen phosphorylase to release glucose-1-phosphate from glycogen... , PHKA2 PHKA2 Phosphorylase b kinase regulatory subunit alpha, liver isoform is an enzyme that in humans is encoded by the PHKA2 gene.-External links:*... |
- | No | No | Yes | None | Delayed motor development, Growth retardation | >- | glucose transporter Glucose transporter Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla... , GLUT2 GLUT2 Glucose transporter 2 also known as solute carrier family 2 , member 2 is a transmembrane carrier protein that enables passive glucose movement across cell membranes. It is the principal transporter for transfer of glucose between liver and blood, and for renal glucose reabsorption... |
Fanconi-Bickel syndrome | Yes | Yes | No | None | >- | Aldolase A | Red cell aldolase deficiency | ? | ? | ? | Exercise intolerance Exercise intolerance Exercise intolerance is a condition where the patient is unable to do physical exercise at the level or for the duration that would be expected of someone in his or her general physical condition, or experiences unusually severe post-exercise pain, fatigue, or other negative effects... , cramps |
>- | β-enolase Enolase Enolase, also known as phosphopyruvate dehydratase, is a metalloenzyme responsible for the catalysis of the conversion of 2-phosphoglycerate to phosphoenolpyruvate , the ninth and penultimate step of glycolysis. Enolase belongs to the class Lyase. Enolase can also catalyze the reverse reaction,... |
- | ? | ? | ? | Exercise intolerance Exercise intolerance Exercise intolerance is a condition where the patient is unable to do physical exercise at the level or for the duration that would be expected of someone in his or her general physical condition, or experiences unusually severe post-exercise pain, fatigue, or other negative effects... , cramps |
Increasing intensity of myalgias Myalgia Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections... over decades |
Serum CK Creatine kinase Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate... : Episodic elevations; Reduced with rest |
>- | glycogen synthase Glycogen synthase Glycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers.... |
- | Yes | No | No | Occasional muscle cramping |