Glycogen storage disease

Glycogen storage disease (GSD, also glycogenosis and dextrinosis) is the result of defects in the processing of glycogen

Glycogen

Glycogen is the molecule that functions as the secondary long-term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by glycogenesis within the brain and stomach...

 synthesis or breakdown within muscle

Muscle

Muscle is the contractile tissue of the body 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 are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...

s) involved in these processes. In livestock, acquired GSD is caused by intoxication

Intoxication

Intoxication is the state of being affected by one or more psychoactive drugs. It can also refer to the effects caused by the ingestion of poison or by the overconsumption of normally harmless substances.Some types of intoxication:*A mechanism of disease....

 with the alkaloid

Alkaloid

Alkaloids are naturally occurring chemical compounds containing basic nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of...

 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....

.

There are eleven distinct diseases that are commonly considered to be glycogen storage diseases (some previously thought to be distinct have been reclassified).

Glycogen storage disease (GSD, also glycogenosis and dextrinosis) is the result of defects in the processing of glycogen

Glycogen

Glycogen is the molecule that functions as the secondary long-term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by glycogenesis within the brain and stomach...

 synthesis or breakdown within muscle

Muscle

Muscle is the contractile tissue of the body 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 are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...

s) involved in these processes. In livestock, acquired GSD is caused by intoxication

Intoxication

Intoxication is the state of being affected by one or more psychoactive drugs. It can also refer to the effects caused by the ingestion of poison or by the overconsumption of normally harmless substances.Some types of intoxication:*A mechanism of disease....

 with the alkaloid

Alkaloid

Alkaloids are naturally occurring chemical compounds containing basic nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of...

 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....

.

Types

There are eleven distinct diseases that are commonly considered to be glycogen storage diseases (some previously thought to be distinct have been reclassified). (Although glycogen synthase

Glycogen synthase

Glycogen synthase is a glycosyltransferase enzyme that catalyses the reaction of UDP-glucose and _n to yield UDP and _n+1.In other words, this enzyme...

 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 recessive
  X-linked recessive
  X-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

Hypoglycemia Hypoglycemia Hypoglycemia or hypoglycaemia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood" Hypoglycemia or hypoglycaemia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally... ?

Hepatomegaly 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... ?

Hyperlipidemia Hyperlipidemia Hyperlipidemia, hyperlipoproteinemia, dyslipidemia or hyperlipidaemia is the presence of raised or abnormal levels of 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

Yes

Yes

Yes

None

Growth failure Growth failure Growth failure is a medical term for a pattern of a child's growth which is poorer than normal for age, sex, stage of maturation, and genetic height expectation. Growth failure usually has an abnormal cause or causes...

Lactic acidosis Lactic acidosis Lactic acidosis is a condition caused by the buildup of lactic acid in the body. It leads to acidification of the blood , and is considered a distinct form of metabolic acidosis. Tissue hypoxia and hypoperfusion force cells to breakdown glucose anaerobically. The result is lactic acid formation... , 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 a neuromuscular, autosomal recessive metabolic disorder in the family of lysosomal storage diseases caused by a deficiency in the enzyme Acid alpha-glucosidase , which is needed to break down glycogen--a long, branched glucose polymer and stored form of sugar...

acid maltase

Pompe's disease

No

Yes

No

Muscle weakness Muscle weakness Muscle weakness, also known as muscle fatigue, is a direct term for the inability to exert force with one's muscles to the degree that would be expected given the individual's general physical fitness. A test of strength is often used during a diagnosis of a muscular disorder before the etiology...

*Death by age ~2 years (infantile variant)

>- | GSD type III Glycogen storage disease type III Glycogen storage disease type III is an autosomal recessive metabolic disorder and inborn error of metabolism, that is characterized by a deficiency in glycogen debranching enzymes....

glycogen debrancher

Cori's disease or Forbe's disease

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...

>- | GSD type IV Glycogen storage disease type IV -Synonyms:It is also known as:-*Glycogenosis type IV,*Glycogen Branching Enzyme Deficiency ,*polyglucosan body disease.*Amylopectinosis-Human pathology:...

glycogen branching enzyme Glycogen branching enzyme A glycogen branching enzyme is an enzyme taking part in the synthesis of glycogen by adding branches to the 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 carbon atoms 1...

Andersen disease

No

hepatosplenomegaly Hepatosplenomegaly Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis or can be the sign of a serious and life threatening lysosomal storage disease.-Common diagnosis:*Farber... , cirrhosis Cirrhosis Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules , leading to progressive loss of liver function...

No

None

Failure to thrive Failure to thrive Failure to thrive is a medical term which denotes poor weight gain and physical growth failure over an extended period of time. Common usage refers to infancy. However, the term is also applied to geriatrics. As used by pediatricians, it covers poor physical growth of any cause and does not imply... , death at age ~5 years

>- | GSD type V Glycogen storage disease type V Glycogen storage disease type V is a metabolic disorder, more specifically a glycogen storage disease, caused by a deficiency of myophosphorylase. It is the most common of the various types of glycogen storage disease, but is still considered rare .GSD type V is also known as McArdle's disease or...

muscle glycogen phosphorylase

McArdle disease

No

No

No

Exercise-induced cramps, Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is the rapid breakdown of skeletal muscle due to injury to muscle tissue. The muscle damage may be caused by physical , chemical, or biological factors...

Renal failure Renal failure Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. It is divided into acute and chronic forms; either form may be due to a large number of other medical problems....  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.It is also known as "Hers' disease", after Henri G. Hers, who characterized it in 1959.-Presentation:...

liver glycogen phosphorylase

Hers' disease

Yes

Yes

No

None

>- | GSD type VII

muscle phosphofructokinase

Tarui's disease

No

No

No

Exercise-induced muscle cramps and weakness (sometimes rhabdomyolysis)

growth retardation

>- | GSD type IX Glycogen storage disease type IX Glycogen storage disease type IX is a form of glycogen storage disease.It is associated with PHKA2, on the X chromosome.-External links:* http://www.agsdus.org/html/typeix.htm...

phosphorylase kinase Phosphorylase kinase Phosphorylase kinase is a serine/threonine-specific protein kinase which converts glycogen phosphorylase b to glycogen phosphorylase a, activating it 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.-Further reading:...

-

No

No

Yes

None

Delayed motor development, Growth retardation

>- | GSD type XI Glycogen storage disease type XI Glycogen storage disease type XI is a form of glycogen storage disease.It is also known as "Fanconi-Bickel syndrome", for Guido Fanconi and Horst Bickel.It is associated with GLUT2....

glucose transporter Glucose transporter Glucose transporters are a family of membrane proteins found in most mammalian cells.-Function:Glucose is an essential substrate for the metabolism of most cells... , 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

>- | GSD type XII

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

>- | GSD type XIII

β-enolase

-

?

?

?

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

>- | GSD type 0 Glycogen storage disease type 0 Glycogen storage disease type 0 is characterized by a deficiency in the glycogen synthase enzyme. Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs because it is another defect of glycogen storage and can cause...

glycogen synthase Glycogen synthase Glycogen synthase is a glycosyltransferase enzyme that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.In other words, this enzyme...

-

Yes

No

No

Occasional muscle cramping