Glycogen storage disease type III
Encyclopedia
Glycogen storage disease type III is an autosomal recessive metabolic disorder and inborn error of metabolism
characterized by a deficiency in glycogen debranching enzymes.
It is also known as Cori's disease in honor of the 1947 Nobel laureates Carl Cori and Gerty Cori
. Other names include Forbes disease in honor of clinician Gilbert Burnett Forbes who further described the features of the disorder, or limit dextrinosis.
Glycogen is a molecule the body uses to store carbohydrate energy. Symptoms of GSD-III are caused by a deficiency of the enzyme amylo-1,6 glucosidase, or debrancher enzyme. This causes excess amounts of an abnormal glycogen to be deposited in the liver, muscles and, in some cases, the heart.
GSD III is inherited in an autosomal recessive pattern, and occurs in about 1 of every 100,000 live births.
The disease typically presents during infancy with hypoglycemia
and failure to thrive
. Clinical examination usually reveals hepatomegaly
. Muscular disease, including hypotonia
and cardiomyopathy
, usually occurs later.
The liver pathology typically regresses as patients enter adolescence
, and few patients develop cirrhosis
during adulthood.
diet, in order to facilitate gluconeogenesis
.
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...
characterized by a deficiency in glycogen debranching enzymes.
It is also known as Cori's disease in honor of the 1947 Nobel laureates Carl Cori and Gerty Cori
Gerty Cori
Gerty Theresa Cori was an American biochemist who became the third woman—and first American woman—to win a Nobel Prize in science, and the first woman to be awarded the Nobel Prize in Physiology or Medicine.Cori was born in Prague...
. Other names include Forbes disease in honor of clinician Gilbert Burnett Forbes who further described the features of the disorder, or limit dextrinosis.
Glycogen is a molecule the body uses to store carbohydrate energy. Symptoms of GSD-III are caused by a deficiency of the enzyme amylo-1,6 glucosidase, or debrancher enzyme. This causes excess amounts of an abnormal glycogen to be deposited in the liver, muscles and, in some cases, the heart.
Genetic prevalence
Presentation
Clinical manifestations are divided into four classes:- GSD IIIa, which clinically includes muscleMuscleMuscle 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...
and liverLiverThe 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...
involvement - GSD IIIb, which clinically has liverLiverThe 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...
involvement but no muscleMuscleMuscle 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...
involvement - GSD IIIc and GSD IIId, which are rarer phenotypes with altered penetrancePenetrancePenetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait . In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms...
The disease typically presents during infancy with hypoglycemia
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"...
and 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 ....
. Clinical examination usually reveals 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...
. Muscular disease, including hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
and cardiomyopathy
Cardiomyopathy
Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
, usually occurs later.
The liver pathology typically regresses as patients enter adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
, and few patients develop 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...
during adulthood.
Treatment
Treatment may involve a high-proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
diet, in order to facilitate gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
.