Glycogen storage disease type IV (GSD IV), or Andersen's Disease, is a form of

glycogen storage disease A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glycolysis, glucose breakdown, typically in m ...

, which is caused by an

inborn error of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrat ...

. It is the result of a mutation in the

GBE1 1,4-alpha-glucan-branching enzyme, also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the ''GBE1'' gene. Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecu ...

gene, which causes a defect in the glycogen branching enzyme. Therefore,

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

is not made properly, and abnormal glycogen molecules accumulate in cells; most severely in cardiac and muscle cells. The severity of this disease varies on the amount of enzyme produced. GSD IV is autosomal recessive, which means each parent has a mutant copy of the gene but shows no symptoms of the disease. Having an autosomal recessive inheritance pattern, males and females are equally likely to be affected by Andersen's disease. Classic Andersen's disease typically becomes apparent during the first few months after the patient is born. Approximately 1 in 20,000 to 25,000 newborns have a glycogen storage disease. Andersen's disease affects 1 in 800,000 individuals worldwide, with 3% of all GSDs being type IV. The disease was described and studied first by

Dorothy Hansine Andersen Dorothy Hansine Andersen (May 15, 1901 – March 3, 1963) was the American physician and researcher who first identified and named cystic fibrosis. During her almost thirty year tenure at Babies Hospital of Columbia-Presbyterian Medical Center ...

Human pathology

It is a result of the absence of the

glycogen branching enzyme 1,4-alpha-glucan-branching enzyme, also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the ''GBE1'' gene. Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecu ...

, which is critical in the production of

. This leads to very long unbranched glucose chains being stored in glycogen. The long unbranched molecules have low solubility, leading to glycogen precipitation in the liver. These deposits subsequently build up in the body tissue, especially the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

and

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. The inability to break down glycogen in muscle cells causes muscle weakness. The probable result is cirrhosis and death within five years. In adults, the enzyme activity is higher and symptoms do not appear until later in life.

Variant types

Fatal perinatal neuromuscular type

* Excess fluid builds up around and in the body of the fetus * Fetuses exhibit

fetal akinesia deformation sequence Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning 'curving of joints' (', 'joint'; ', late Latin form of late Greek ', 'hooking'). Children born with one ...

* Causes a decrease in fetal movement and stiffness of joints after birth * Infants have low muscle tone and muscle wasting * Do not survive past the newborn stage due to weakened heart and lungs

Congenital muscular type

* Develops in early infancy * Babies have dilated cardiomyopathy, preventing the heart from pumping efficiently * Only survive a few months

Progressive hepatic type

* Infants have difficulty gaining weight * Develop enlarged liver and cirrhosis that is irreversible * High BP in the hepatic portal vein and buildup of fluid in the abdominal cavity * Die of liver failure in early childhood

Non-progressive hepatic type

* Same as progressive, but liver disease is not so severe * Do not usually develop cirrhosis * Usually shows muscle weakness and hypotonia * Survive into adulthood * Life expectancy varies upon symptom severity

Childhood neuromuscular type

* Develops in late childhood * Has myopathy and dilated cardiomyopathy * Varies greatly * Some have mild muscle weakness * Some have severe cardiomyopathy and die in early adulthood

Diagnosis

An assay of amylo-1,4 → 1,6 glucan transferases (which removes a block of 6 glucose residues from the 1,4 position and attaches it to the 1,6 position of the same chain)

Alternative names and related disease

Alternative names in medical literature for the disease include: * Andersen's triad * Glycogenosis type IV * Glycogen branching enzyme deficiency * Polyglucosan body disease * Amylopectinosis Mutations in GBE1 can also cause a milder disease in adults that is called

adult polyglucosan body disease Adult polyglucosan body disease (APBD) is a rare monogenic glycogen storage disorder ( GSD type IV) caused by an inborn error of metabolism. Symptoms can emerge any time after the age of 30. Early symptoms include trouble controlling urinatio ...

In other mammals

The form in horses is known as

glycogen branching enzyme deficiency Glycogen-branching enzyme deficiency (GBED) is an inheritable glycogen storage disease affecting American Quarter Horses and American Paint Horses. It leads to abortion, stillbirths, or early death of affected animals. The human form of the disease ...

. It has been reported in

American Quarter Horse The American Quarter Horse, or Quarter Horse, is an American breed of horse that excels at sprinting short distances. Its name is derived from its ability to outrun other horse breeds in races of or less; some have been clocked at speeds up to ...

s and related breeds. The disease has been reported in the Norwegian Forest Cat, where it causes skeletal muscle, heart, and CNS degeneration in animals greater than five months old. It has not been associated with

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

or liver failure. "Deficiency of glycogen branching enzyme (GBE) activity causes glycogen storage disease type IV (GSD IV), an autosomal recessive error of metabolism. Abnormal glycogen accumulates in myocytes, hepatocytes, and neurons, causing variably progressive, benign to lethal organ dysfunctions. A naturally occurring orthologue of human GSD IV was described previously in Norwegian Forest cats (NFC)."

References

External links

* {{Carbohydrate metabolic pathology Inborn errors of carbohydrate metabolism Hepatology