Glycogen storage disease type IV
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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 an enzyme deficiency affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells. GSD has ...
, 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 molecul ...
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. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...
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 show no symptoms of the disease. It 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 an American physician, pediatrician, and pathologist who was the first person to identify cystic fibrosis, the first to describe the disease, and the one to name it. in 1939, she was a ...
.


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 molecul ...
, which is critical in the production of
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...
. 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 in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
and
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. 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 activity of the enzyme 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 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 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 show 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 genetic glycogen storage disorder caused by an inborn error of metabolism. Symptoms can emerge any time after the age of 30; early symptoms include trouble controlling urination, trouble walking ...
.


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 a quarter mile or less; some have been clocked at s ...
s and related breeds. The disease has been reported in the
Norwegian Forest Cat The Norwegian Forest cat ( no, Norsk skogskatt and ) is a breed of domestic cat originating in Northern Europe. This natural breed is adapted to a very cold climate, with a top coat of long, glossy, water-shedding hair and a woolly undercoat f ...
, 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, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
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