Glycogen Storage Disease

Excerpt

Glycogen storage diseases (GSDs) are inherited inborn errors of carbohydrate metabolism that result in abnormal glycogen storage. The onset can range from neonatal life to adulthood, and clinical manifestations result either from a failure to convert glycogen into energy or the toxic accumulation of glycogen.

Glycogen is a branched polymer comprised of glucose monomers (see Image. Glycogen, Free Glucose Release, and Glycogen Storage Diseases, Figure 1). After a meal, the plasma glucose level rises, stimulating the storage of the excess in cytoplasmic glycogen.

The liver contains the highest percentage of glycogen by weight (about 10%), whereas muscles can store about 2% by weight. Nevertheless, since the total muscle mass is greater than the liver mass, the total mass of glycogen in muscles is about twice that of the liver. When needed, the glycogen polymer can be broken down into glucose monomers and utilized for energy production. Defects in the enzymes and transporters for these processes cause GSDs. An increasing number of GSDs are being identified, but most are very rare. These subtypes are classified numerically in the order of recognition and identification of the enzyme defect causing the disorder.

Classification of Glycogen Storage Disorder

GSDs that primarily affect the liver include the following:

1. Glycogen synthase-2 deficiency (GSD type 0a)

2. Glucose-6-phosphatase deficiency (GSD type Ia)

3. Glucose-6-phosphate transporter deficiency (GSD type Ib)

4. Glycogen debrancher deficiency (GSD type III)

5. Glycogen branching enzyme deficiency (GSD type IV)

6. Liver phosphorylase deficiency (GSD type VI)

7. Phosphorylase kinase deficiency (GSD type IXa)

8. GLUT2 deficiency or Fanconi-Bickel disease

GSDs that primarily affect the skeletal muscles include the following:

1. Muscle phosphorylase deficiency (GSD type V)

2. Phosphofructokinase deficiency (GSD type VII)

3. Phosphoglycerate mutase deficiency (GSD type X)

4. Lactate dehydrogenase A deficiency (GSD type XI)

5. Aldolase A deficiency (GSD type XII)

6. β-enolase deficiency (GSD type XIII)

7. Phosphoglucomutase-1 deficiency (GSD type XIV)

GSDs that affect both skeletal and cardiac muscles include the following:

1. Lysosomal acid maltase deficiency (GSD type IIa)

2. Lysosome-associated membrane protein 2 deficiency (GSD type IIb)

3. Glycogenin-1 deficiency (GSD type XV)

4. Muscle glycogen synthase deficiency (GSD type 0b)