Glycogen storage disease type III

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Glycogen storage disease type III
Other namesCori Disease, Debrancher Deficiency, Forbes Disease [1]
Glycogen storage disease in liver - high mag.jpg
Micrograph of glycogen storage disease with histologic features consistent with Cori disease. Liver biopsy. H&E stain.
Specialty Endocrinology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Hypotonia [2]
CausesAGL gene mutation [3]
Diagnostic method Biopsy, Elevated transaminases [4]
TreatmentCurrently no cure, Diet regime [4]

Glycogen storage disease type III (GSD III) is an autosomal recessive metabolic disorder and inborn error of metabolism (specifically of carbohydrates) characterized by a deficiency in glycogen debranching enzymes. [3] 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 (1915–2003), an American physician who further described the features of the disorder, or limit dextrinosis, due to the limit dextrin-like structures in cytosol. [2] Limit dextrin is the remaining polymer produced after hydrolysis of glycogen. Without glycogen debranching enzymes to further convert these branched glycogen polymers to glucose, limit dextrinosis abnormally accumulates in the cytoplasm. [5]

Contents

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.[ medical citation needed ]

Signs and symptoms

Glycogen storage disease type III 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 the individual enters adolescence, as does splenomegaly, should the individual so develop it. [2]

Genetics

GSD III is AR Autorecessive.svg
GSD III is AR

In regards to genetics glycogen storage disease type III is inherited in an autosomal recessive pattern (which means both parents need be a carrier), and occurs in about 1 of every 100,000 live births. The highest incidence of glycogen storage disease type III is in the Faroe Islands where it occurs in 1 out of every 3,600 births, probably due to a founder effect. [6]

There seem to be two mutations in exon 3 (c.17_18delAG) being one of them, which are linked to the subtype IIIb. [1] [7]

The amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase gene and mutations to it, are at the root of this condition. The gene is responsible for creating glycogen debranching enzyme, which in turn helps in glycogen decomposition. [3] [8]

Diagnosis

In terms of the diagnosis for glycogen storage disease type III, the following tests/exams are carried out to determine if the individual has the condition: [9] [10]

Differential diagnosis

The differential diagnosis of glycogen storage disease type III includes GSD I, GSD IX and GSD VI. This however does not mean other glycogen storage diseases should not be distinguished as well. [1]

Classification

Clinical manifestations of glycogen storage disease type III are divided into four classes: [3]

Treatment

Glucose Alpha-D-glucopyranose-2D-skeletal.svg
Glucose

Treatment for glycogen storage disease type III may involve a high-protein diet, in order to facilitate gluconeogenesis. Additionally the individual may need: [2] [1] [10]

Related Research Articles

<span class="mw-page-title-main">Glycogen storage disease</span> Medical condition

A glycogen storage disease is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells.

<span class="mw-page-title-main">Gaucher's disease</span> Medical condition

Gaucher's disease or Gaucher disease (GD) is a genetic disorder in which glucocerebroside accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase, which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages. Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.

<span class="mw-page-title-main">Glycogen storage disease type II</span> Medical condition

Glycogen storage disease type II(GSD-II), also called Pompe disease, and formerly known as GSD-IIa or Limb–girdle muscular dystrophy2V, 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 (GAA). The inability to breakdown glycogen within the lysosomes of cells leads to progressive muscle weakness throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and the nervous system.

<span class="mw-page-title-main">Phosphofructokinase deficiency</span> Medical condition

Phosphofructokinase deficiency is a rare muscular metabolic disorder, with an autosomal recessive inheritance pattern.

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 (substrates) into others (products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or due to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are often referred to as congenital metabolic diseases or inherited metabolic disorders. Another term used to describe these disorders is "enzymopathies". This term was created following the study of biodynamic enzymology, a science based on the study of the enzymes and their products. Finally, inborn errors of metabolism were studied for the first time by British physician Archibald Garrod (1857–1936), in 1908. He is known for work that prefigured the "one gene–one enzyme" hypothesis, based on his studies on the nature and inheritance of alkaptonuria. His seminal text, Inborn Errors of Metabolism, was published in 1923.

<span class="mw-page-title-main">Glycogen phosphorylase</span> Class of enzymes

Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects.

<span class="mw-page-title-main">Glycogen storage disease type I</span> Medical condition

Glycogen storage disease type I is an inherited disease that prevents the liver from properly breaking down stored glycogen, which is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. There are also possibly rarer subtypes, the translocases for inorganic phosphate or glucose ; however, a recent study suggests that the biochemical assays used to differentiate GSD Ic and GSD Id from GSD Ib are not reliable, and are therefore GSD Ib.

<span class="mw-page-title-main">Glycogen debranching enzyme</span> Mammalian protein found in Homo sapiens

The glycogen debranching enzyme, in humans, is the protein encoded by the gene AGL. This enzyme is essential for the breakdown of glycogen, which serves as a store of glucose in the body. It has separate glucosyltransferase and glucosidase activities.

<span class="mw-page-title-main">Glycogen storage disease type IV</span> Human disease

Glycogen storage disease type IV (GSD IV), or Andersen's Disease, is a form of glycogen storage disease, which is caused by an inborn error of metabolism. It is the result of a mutation in the GBE1 gene, which causes a defect in the glycogen branching enzyme. Therefore, glycogen 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. 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.

<span class="mw-page-title-main">Glycogen storage disease type 0</span> Medical condition

Glycogen storage disease type 0 is a disease characterized by a deficiency in the glycogen synthase enzyme (GSY). Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a glycogen storage disease because it is another defect of glycogen storage and can cause similar problems. There are two isoforms (types) of glycogen synthase enzyme; GSY1 in muscle and GSY2 in liver, each with a corresponding form of the disease. Mutations in the liver isoform (GSY2), causes fasting hypoglycemia, high blood ketones, increased free fatty acids and low levels of alanine and lactate. Conversely, feeding in these patients results in hyperglycemia and hyperlactatemia.

<span class="mw-page-title-main">Glucose 6-phosphatase</span> Enzyme

Boron, Walter F.; Boulpaep, Emile L., eds. (2017). Medical Physiology (3rd ed.). Philadelphia, PA: Elsevier. ISBN 978-1-4557-4377-3.

<span class="mw-page-title-main">Glycogen branching enzyme</span> Mammalian protein involved in glycogen production

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.

<span class="mw-page-title-main">Acid alpha-glucosidase</span> Protein-coding gene in the species Homo sapiens

Acid alpha-glucosidase, also called acid maltase, is an enzyme that helps to break down glycogen in the lysosome. It is functionally similar to glycogen debranching enzyme, but is on a different chromosome, processed differently by the cell and is located in the lysosome rather than the cytosol. In humans, it is encoded by the GAA gene. Errors in this gene cause glycogen storage disease type II.

<span class="mw-page-title-main">Myophosphorylase</span> Muscle enzyme involved in glycogen breakdown

Myophosphorylase or glycogen phosphorylase, muscle associated (PYGM) is the muscle isoform of the enzyme glycogen phosphorylase and is encoded by the PYGM gene. This enzyme helps break down glycogen into glucose-1-phosphate, so it can be used within the muscle cell. Mutations in this gene are associated with McArdle disease, a glycogen storage disease of muscle.

<span class="mw-page-title-main">PHKG2</span> Protein-coding gene in the species Homo sapiens

Phosphorylase b kinase gamma catalytic chain, testis/liver isoform is an enzyme that in humans is encoded by the PHKG2 gene.

<span class="mw-page-title-main">Glycogen storage disease type IX</span> Medical condition

Glycogen storage disease type IX is a hereditary deficiency of glycogen phosphorylase kinase B that affects the liver and skeletal muscle tissue. It is inherited in an X-linked or autosomal recessive manner.

<span class="mw-page-title-main">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

Danon disease is a metabolic disorder. Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability. It is inherited in an X-linked dominant pattern.

<span class="mw-page-title-main">Metabolic myopathy</span> Type of myopathies

Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects that interfere with the ability to create energy, causing a low ATP reservoir within the muscle cell.

Barbara Illingworth Brown was an American biochemist. She worked primarily at Washington University in St. Louis.

References

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Further reading