Type V Glycogen Storage Disease

Updated: May 02, 2022
  • Author: Isaac Omolade Ogunmola, MBBS; Chief Editor: George T Griffing, MD  more...
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Practice Essentials

glycogen storage disease (GSD) is the result of an enzyme defect. These enzymes normally catalyze reactions that ultimately convert glycogen compounds to glucose. Enzyme deficiency results in glycogen accumulation in tissues. In many cases, the defect has systemic consequences, but in some cases, the defect is limited to specific tissues. Most patients experience muscle symptoms, such as weakness and cramps, although certain GSDs manifest as specific syndromes, such as hypoglycemic seizures or cardiomegaly.

The diagram below illustrates metabolic pathways of carbohydrates.

Metabolic pathways of carbohydrates. Metabolic pathways of carbohydrates.

The following list contains a quick reference for 8 of the GSD types:

  • 0 - Glycogen synthase deficiency

  • Ia - Glucose-6-phosphatase deficiency (von Gierke disease)

  • II - Acid maltase deficiency (Pompe disease)

  • III - Debranching enzyme deficiency (Forbes-Cori disease)

  • IV - Transglucosidase deficiency (Andersen disease, amylopectinosis)

  • V - Myophosphorylase deficiency (McArdle disease)

  • VI - Phosphorylase deficiency (Hers disease)

  • VII - Phosphofructokinase deficiency (Tarui disease)

Although at least 14 unique GSDs are discussed in the literature, the 4 that cause clinically significant muscle weakness are Pompe disease (GSD type II, acid maltase deficiency), Cori disease (GSD type III, debranching enzyme deficiency), McArdle disease (GSD type V, myophosphorylase deficiency), and Tarui disease (GSD type VII, phosphofructokinase deficiency). One form, von Gierke disease (GSD type Ia, glucose-6-phosphatase deficiency), causes clinically significant end-organ disease with significant morbidity. The remaining GSDs are not benign but are less clinically significant; therefore, the physician should consider the aforementioned GSDs when initially entertaining the diagnosis of a GSD. Interestingly, GSD type 0 also is described and is a disorder causing glycogen deficiency due to defective glycogen synthase.

These inherited enzyme defects usually present in childhood, although some, such as McArdle disease and Pompe disease, have separate adult-onset forms. In general, GSDs are inherited as autosomal recessive conditions. Several different mutations have been reported for each disorder. [1]


Diagnosis depends on findings from patient history and physical examination, creatine kinase testing, muscle biopsy, electromyelography, and ischemic forearm testing. Biochemical assay for enzyme activity is the method of definitive diagnosis.

Myophosphorylase, the deficient enzyme in McArdle disease, is found in muscle tissue. Myophosphorylase deficiency causes muscle cramps, pain, and stiffness. One hallmark of McArdle disease is weakness with exertion. Proximal muscle weakness may progress with time, and no specific treatment exists.


Unfortunately, no specific treatment or cure exists for GSDs, although diet therapy may be highly effective at reducing clinical manifestations. In some cases, liver transplantation may abolish biochemical abnormalities. Active research continues.

Patient education

Genetic counseling is appropriate for all individuals with a genetic disorder.



The phenotype of the individual with GSD results from an enzyme defect. Carbohydrate metabolic pathways are blocked, leading to excess glycogen accumulation in affected tissues and/or disturbances in energy production. Several gene mutations have been described. [1]

Fatty acids and glucose serve as substrates for energy production. With intense exercise, glucose from glycogen stores in muscle becomes the predominant resource. Fatigue develops when the glycogen supply is exhausted. [2, 3] Each GSD represents a specific enzyme defect, and each enzyme is in specific, or most, body tissues. Myophosphorylase is found in muscle. Hypoglycemia is not an expected finding because liver phosphorylase is not involved.

GSD type V is an autosomal recessive disease resulting from mutations in the PYGM gene that encodes for the muscle isoform of glycogen phosphorylase (myophosphorylase). Heterozygotes usually do not manifest clinical features of the disease. [1]



International statistics

Herling and colleagues studied the incidence and frequency of inherited metabolic conditions in British Columbia. GSDs are found in 2.3 children per 100,000 births per year. The prevalence of GSD type V is estimated to be around 1 in 100,000–140,000 persons.  [1]

Age-related demographics

In general, GSDs present in childhood. Later onset correlates with a less severe form. Consider Pompe disease if onset is in infancy.

The majority of patients with McArdle disease present in the second to third decade of life.

Cheraud and colleagues report two unique cases of McArdle disease presenting in individuals in their seventies. Physicians should have clinical suspicion regardless of age of presentation. [4]



The life expectancy of patients with McArdle disease is typically not affected. [1]  Pregnancy and childbirth outcomes are relatively unaffected by the disease. [5]


Immediate morbidity arises from severe exercise intolerance.


There are potential anesthetic and perioperative risks. [6]