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Glycogen Storage Disease, Type VI
Updated: Sep 21, 2007
Introduction
Background
A 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 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 (Tauri 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 necessarily 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, which is due to defective glycogen synthase.
These inherited enzyme defects usually present in childhood, although some, such as McArdle disease and Pompe disease (also known as acid maltase deficiency), have separate adult-onset forms. In general, GSDs are inherited as autosomal recessive conditions. Several different mutations recently have been reported for each disorder.
Unfortunately, no specific treatment or cure exists, although diet therapy may be highly effective at reducing clinical manifestations. In some cases, liver transplantation may abolish biochemical abnormalities. Active research continues.
Diagnosis depends on findings from patient history and physical examination, muscle biopsy, electromyography, ischemic forearm testing, and creatine kinase testing. Biochemical assay for enzyme activity is the method of definitive diagnosis.
In patients with Hers disease, defective liver phosphorylase results in hepatomegaly and hypoglycemia. The liver phosphorylase enzyme is found within the liver and red blood cells.
Pathophysiology
With an enzyme defect, carbohydrate metabolic pathways are blocked and excess glycogen accumulates in affected tissues. Each GSD represents a specific enzyme defect, and each enzyme is in specific, or most, body tissues. Liver phosphorylase, which is found in the liver and red blood cells, is deficient, which results in glycogen accumulation in the liver and subsequent hypoglycemia.
Several mutations of the liver glycogen phosphorylase gene are reported.
Frequency
International
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.
Mortality/Morbidity
Morbidity results from consequences of hepatomegaly.
Age
In general, GSDs present in childhood. Later onset correlates with a less severe form. Consider Pompe disease if onset is in infancy.
Clinical
History
- Symptoms result from mild hypoglycemia.
- No specific symptoms are associated with Hers disease (glycogen storage disease, type VI).
Physical
- Hepatomegaly may be present; however, because many causes of hepatic injury exist, suspicion must be high.
- Growth retardation is possible.
Causes
- The liver isoform of phosphorylase is deficient.
- A mutation has been mapped to chromosome 14. A splicing site mutation has been identified.
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References
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Further Reading
Keywords
Hers disease, glycogen storage disease type VI, GSD type VI, enzyme defect, hepatomegaly, hypoglycemia, liver phosphorylase deficiency, glycogen storage disease, GSD, Hers' disease, GSD type 0, glycogen synthase deficiency, GSD type Ia, glucose-6-phosphatase deficiency, G-6-P deficiency, von Gierke disease, GSD type II, acid maltase deficiency, Pompe disease, GSD type III, debranching enzyme deficiency, Forbes-Cori disease, GSD type IV, GSD type V, myophosphorylase deficiency, McArdle disease, transglucosidase deficiency, Andersen disease, amylopectinosis, GSD type VII, phosphofructokinase deficiency, Tauri disease
