Monografias Y Ensayos

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Glycogen Storage Disease, Type II (Pompe Disease) 
Background
A glycogen storage disease (GSD) is the result of an enzyme defect. These enzymes normally catalyze reactions that ultimately convert glycogen compounds to monosaccharides, of which glucose is the predominant component. Enzyme deficiency results in glycogen accumulation in tissues.In many cases, the defect has systemic consequences; however, 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.
Although at least 14 unique GSDs are discussed in the literature, the 4 that cause clinically significantmuscle 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 significantmorbidity. 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, a GSD type 0 also exists and is due to defective glycogen synthase.
The chart below demonstrates where various forms of GSD affect the metabolic carbohydrate pathways.
Glycogen storagedisease, type II. 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 (Andersendisease, amylopectinosis)
* V - Myophosphorylase deficiency (McArdle disease)
* VI - Phosphorylase deficiency (Hers disease)
* VII - Phosphofructokinase deficiency (Tarui disease)
These inherited enzyme defects usually manifest in childhood, although some, such as McArdle disease and Pompe disease, have separate adult-onset forms. In general, GSDs are inherited as autosomal recessiveconditions. Several different mutations 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 patients, liver transplantation may abolish biochemical abnormalities. Active research continues.
Diagnosis depends on muscle biopsy, electromyelography, the ischemic forearm test,creatine kinase levels, patient history, and physical examination findings. Biochemical assay for enzyme activity is the method of definitive diagnosis.[1]
Acid maltase catalyzes the hydrogenation reaction of maltose to glucose. Acid maltase deficiency is a unique glycogenosis in that the glycogen accumulation is lysosomal rather than in the cytoplasm. It also has a unique clinical presentationdepending on age at onset, ranging from fatal hypotonia and cardiomegaly in the neonate to muscular dystrophy in adults.
Pompe disease represents about 15% of all GSDs based on combined European and American data.
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 either in specific sites or is in most body tissues.
Acid maltase is a lysosomal enzyme that catalyzes the hydrogenation of branched glycogen compounds, notably maltose, to glucose. The conversion generally is a one-way reaction from glycogen to glucose-6-phosphate. When acid maltase is deficient, glycogen accumulates within tissues. Acid maltase is found in all tissues,...