| disease | Glycogen Storage Disease |
| alias | Glycogen Storage Disease, GSD |
Glycogen storage disease refers to a group of disorders characterized by excessive glycogen accumulation in tissues, with various types caused by inherited enzyme deficiencies or abnormal glycogen structure.
bubble_chart Etiology
1. Glycogen storage disease type III: The disease cause is a deficiency of amylo-1,6-glucosidase (debranching enzyme) in the liver and muscles. After glycogen is broken down by phosphorylase, it cannot be further completely degraded into glucose.
2. Glycogen storage disease type IV: Caused by a deficiency of amylo-(1,4-1,6)-transglucosidase (branching enzyme). The stored glycogen has an abnormal structure, with long outer chains and reduced branching, resembling amylopectin, hence it is also called amylopectinosis. The solubility of the stored abnormal glycogen is much lower than that of normal glycogen. This disease is rare and inherited in an autosomal recessive manner. Heterozygous individuals exhibit molecular enzyme defects in fibroblasts.
Glycogen storage disease is classified into at least 12 types, among which type 0 (glycogen synthesis deficiency) and type IV (amylo-1,4-1,6-transglucosidase deficiency) can lead to liver cirrhosis and liver failure. Type I (glucose-6-phosphatase deficiency) may progress to benign liver adenoma and adenocarcinoma, while type III (amylo-1,6-glucosidase deficiency, debranching enzyme deficiency) can develop into liver fibrosis or cirrhosis.
bubble_chart Pathological Changes
1. Glycogen Storage Disease Type III This type is characterized by: ① hepatic fibrous septa; ② absence of fat deposition, which distinguishes it from GSD-I. In GSD-III, cirrhosis often occurs when there are simultaneous deficiencies in two or more enzymes, i.e., in addition to debranching enzyme deficiency, there may also be deficiencies in phosphatase and/or phosphokinase. Compared to GSD-I, the ultrastructure of GSD-III shows smaller and fewer fat droplets. Besides liver lesions, glycogen also accumulates in muscles.
2. Glycogen Storage Disease Type IV In this type, the liver exhibits micronodular cirrhosis with broad fibrous bands surrounding or penetrating the hepatic lobules. Grade I bile duct hyperplasia is observed in the portal areas. Pale amphophilic or basophilic staining material deposits in hepatocytes, myocardial cells, skeletal muscle cells, and brain cells. Eosinophilic or colorless inclusions can be found in the cytoplasm of periportal hepatocytes, displacing the nucleus to one side, forming the characteristic sexually transmitted disease changes of GSD-IV. Histochemical staining reveals that the deposits in hepatocytes are abnormal glycogen.bubble_chart Clinical Manifestations
1. Glycogen Storage Disease Type III
Physical examination alone is difficult to distinguish from GSD-I. Hepatomegaly and developmental delays are prominent in infancy, and some children may develop splenomegaly between ages 4–6. These patients may show evidence of liver fibrosis but do not necessarily progress to cirrhosis or liver failure.
In addition to liver involvement, most patients experience muscle weakness, especially during running or climbing, but do not develop muscle fleshy rigidity. Some patients exhibit muscle atrophy. Glycogen may accumulate in the heart, leading to cardiomegaly. Electrocardiograms show nonspecific changes, but heart failure and arrhythmias do not occur, and the kidneys remain normal in size.
Hypoglycemia is milder than in GSD-I, and the liver tends to shrink during adolescence. Only those with phosphatase or phosphorylase deficiency progress to cirrhosis.
2. Glycogen Storage Disease Type IV
Infants are often asymptomatic for the first few months after birth, with subtle symptoms appearing within the first year. The earliest symptoms may appear at 3 months, and the latest at 15 months. Nonspecific gastrointestinal symptoms, hepatosplenomegaly, liver dysfunction, growth retardation, and signs such as hypotonia and muscle atrophy may occur. As the disease progresses, abdominal varices, cirrhosis with portal hypertension, ascites, and esophageal varices may develop. The survival period after diagnosis is typically 2–37 months, occasionally 3–4 years, with most patients eventually succumbing to chronic liver failure, upper consumptive thirst gastrointestinal bleeding, heart failure, or infection.
1. Glycogen Storage Disease Type III
This type is characterized by elevated blood lipids, the degree of which correlates with the extent of blood glucose reduction, though the increase in blood lipids is less pronounced than in GSD-I. A few patients exhibit grade I hyperuricemia and elevated serum transaminases (300–600 IU).
The conversion of galactose, sucrose, amino acids, and proteins into glucose proceeds normally, so these foods can raise blood glucose levels. The response to fasting adrenaline or glucagon is poor, but if the adrenaline or glucagon test is performed several hours after eating, the response is normal.
2. Glycogen Storage Disease Type IV
Serum transaminases and alkaline phosphatase are elevated, with grade I hypercholesterolemia in advanced stages. Following the onset of liver failure, a series of changes may occur, such as hypoalbuminemia, elevated bilirubin, increased globulin, and alterations in blood ammonia. The glucagon and adrenaline tolerance tests yield a positive blood glucose response, raising blood glucose by 0.83 mmol/L to 1.28 mmol/L, with the peak occurring 30 minutes after injection. Oral glucose and sucrose tolerance tests are normal. Serum lactate and pyruvate levels are normal.
Glycogen storage disease type III is diagnosed through enzyme analysis, and based on the results of enzyme analysis, GSD-III can be classified into different subtypes.
bubble_chart Treatment Measures
1. Glycogen Storage Disease Type III
A high-protein diet can improve growth and muscle strength, but recent studies suggest that a high-starch, standard-protein diet is more effective.
There is no specific treatment. A high-protein, low-carbohydrate diet supplemented with corn oil has failed to halt the progression of liver cirrhosis. The use of purified glucagon has not yielded definitive results. Extracts from Aspergillus species can drastically reduce liver glycogen, making it a promising therapeutic approach for further research. Additionally, liver transplantation may be performed.
