Glycogen Storage Disease

Excerpt

Glycogen storage diseases (GSDs) are inherited inborn errors of carbohydrate metabolism. Disorders of carbohydrate metabolism that result in abnormal storage of glycogen are classified as GSDs. They are classified numerically in the order of recognition and identification of the enzyme defect causing the disorder. Clinical onset can range from neonatal life to adulthood. Depending on the specific type, GSDs can result from a failure to convert glycogen into energy and/or a toxic glycogen accumulation; however, all result in a failure to use or store glycogen.

Glycogen is a branched polymer whose monomeric units are glucose (Figure 1). After a meal, the glucose level in plasma increases and stimulates the storage of excess glucose in cytoplasmic glycogen. The liver contains the highest percent of glycogen by weight (about 10%), whereas muscles can store about 2% by weight. Nevertheless, since the total muscle mass is greater than liver mass, the total mass of glycogen in the muscle is about twice that of the liver. When needed, the glycogen polymer can be broken down into glucose monomers and utilized for energy production. Many of the enzymes and transporters for these processes are key to the etiology of GSDs. An increasing number of GSDs are being identified, but most are very rare. Traditionally the GSDs were named after the clinician who first identified the disorder; however, they each have an identified enzyme and gene focus that will be used to refer to these disorders in this article, although the various diseases have their own classifications.

Classification of Glycogen Storage Disorder

Glycogen storage disorders that primarily affect the liver include:

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

Glycogen storage disorders that primarily affect the skeletal muscles include:

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. Beta-enolase deficiency (GSD type XIII)

7. Phosphoglucomutase-1 deficiency (GSD type XIV)

Glycogen storage disorders that affect both skeletal and cardiac muscles include:

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)