Introduction
Glycogen storage device type 13 is a metabolic disorder of glucose metabolism. It is also known as beta enolase deficiency. It is a rare genetic disease that occurs due to a defect in the enzyme that breaks down glucose. The first case of the disorder was reported in 2001. The inherited metabolic disorder is due to the mutations in the gene ENO3 that result in beta enolase deficiency in the muscles. Enolase enzyme helps in the metabolism of glycolysis, mainly in anaerobic glycolysis. Enolase deficiency can result in hemolytic anemia. It is a genetic disorder but can be transmitted through an autosomal inheritance pattern. The beta subunit of beta enolase is mainly found in the muscles. The condition involves the muscles, leading to muscle weakness after exercise, muscle dystrophy, and myalgia (pain in a group of muscles). The affected person's muscles cannot produce energy, leading to pain and muscle weakness. Like other glycolytic enzyme deficiencies, beta enolase deficiency is also involved in red blood cells. The disorder is mainly seen in caucasian people.
What Are the Causes of Beta-Enolase Deficiency?
Genetic Cause: It is the most common cause of beta-enolase deficiency and can be inherited from the parent. The individual with the enzyme deficiency can be heterozygous for the beta enolase gene and carry two mutated genes. Therefore, one gene can be inherited from each parent. The child's muscle cells may synthesize two forms of beta enolase; each enzyme carries different mutations. These mutations can change the position of glycine at 156 to glutamate and the place of glycine at 374 to aspartate. Changes in the position of mutated genes in the muscles can lead to muscle weakness.
What Is the Structure of the Beta Enolase Enzyme?
The enzyme enolase consists of three subunits and a different gene encodes each subunit. The alpha subunit is involved in early embryo development and several other adult tissues, whereas the beta subunit involved in beta enolase deficiency is encoded by the gene ENO3, mainly found in the muscles. On the other hand, the gamma subunit is primarily found in the nervous tissue.
What Are the Functions of the Enolase Enzyme?
Enzyme enolase is involved in anaerobic glycolysis. For example, the enzyme ENO3 catalyzes the reversible conversion of phosphoglycerate to phosphoenolpyruvate. The isoform is expressed in the skeletal, striated, and cardiac muscles. During muscle development in the fetus, there is a transcriptional switch of gene ENO1 to ENO3. In fast-twitch fibers, higher levels of ENO3 are present than in low-twitch threads.
What Is the Mechanism of Action of Enolase in Beta Enolase Deficiency?
The enolase enzyme is involved in converting the ninth step of glycolysis from 2-phosphoglycerate to phosphoenolpyruvate. Enolase consists of three subunits that are alpha, beta, and gamma. The tissues need large amounts of energy; the enolase form of alpha gamma in the brain and alpha beta in the striated muscles provide power. However, beta enolase is only found in the striated muscles.
The two mutations in the ENO3 gene are responsible for the enolase deficiency. In addition, the change in the positions of amino acids from glycine 374 to aspartate and at 156 to glutamate may change the enzyme's structure. The mutations may reduce the level of the proteins in the muscles and impair the functions of the muscles.
Glycogen is stored in the muscle tissue. It is an essential source of energy for the muscles during exercise and movement. The enolase enzyme from the gene ENO3 helps the strength to use glycogen for power. In glycogen storage disorder type 13, the body cannot make enough enolase due to the mutation in the gene ENO3. As a result, the muscle does not have enough power to work correctly. Therefore, the disorder mainly involves the forces leading to muscle weakness.
What Are the Signs and Symptoms of Beta Enolase Deficiency?
The onset of the symptoms is in adulthood. The signs and symptoms of beta enolase deficiency include
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Generalized muscle weakness.
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Vomiting.
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Myopathy (dysfunction of muscle fiber leading to muscle weakness).
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Hemolytic anemia (low number of red blood cells).
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Reduced muscle mass.
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Exercise intolerance.
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Easy muscle fatigue.
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Myalgia (pain in a group of muscles).
How Can Beta Enolase Deficiency Be Diagnosed?
Gene ENO3 makes a chemical known as enolase, which helps produce energy in the muscles. The doctor may diagnose the condition by taking a biopsy. First, the doctor may take a sample from the muscle tissue to determine the percentage of enolase chemicals working in the muscle tissue. Then, the physician may recommend laboratory tests for genetic testing. Next, the laboratory personnel can do genetic testing for gene mutation in the ENO3 gene. Finally, the doctor may diagnose the condition by clinically checking symptoms like exercise intolerance and myalgia.
How Can Beta Enolase Deficiency Be Managed?
The main goal of the treatment is to prevent metabolic disarrangements. In addition, a change in dietary habits may improve muscle strength and weakness. Initially, the doctor may prescribe carbohydrate-enriched meals during the day and night. Next, calcium, potassium, and magnesium intake may increase muscle strength. Then, the physiotherapist may help with resistive exercise to help strengthen the muscles and recommend stretching exercises to prevent muscle stiffness.
The doctor may administer bronchodilators and oxygen supplementation in case of exercise intolerance and advise the patient to do lighter exercises. It will help in changing the patient's routine. In case of severe symptoms, the surgeon may recommend surgery.
Conclusion
Glycogen storage disease type 13 is a rare metabolic and genetic disorder. The condition is due to a mutation in the gene ENO3 and a deficiency of the muscle that takes part in anaerobic glycolysis. The transformation can lead to muscle weakness and myalgia because the enzyme enolase is present in the muscles. The patient cannot do exercise due to pain in the muscle. Healthcare providers may prescribe dietary supplements like carbohydrates, calcium, and potassium to improve muscle weakness and strength. In addition, the physiotherapist may recommend the patient do stretching and lighter exercises to improve muscle stiffness.
