Glycogen storage disease

Introduction to glycogen storage disease Glycogenstoragedise (glycogenstoragedisease) is a group of hidden glycogens in the tissue due to the lack of certain enzymes in the glycogen metabolism of liver, muscle and brain tissue, which can not be normally decomposed or synthesized in tissues. Sexually inherited glycogen metabolism disorders, also known as glycogen disease (glycogendisease), glycogen metabolism (glycogenoses). The disease was first discovered in 1928 by several doctors in the Netherlands in 1929. Most of them were lack of glycogenolytic enzymes. The glycogen was decomposed in tissues and deposited too much. Very few were due to lack of glycogen synthase. The glycogen storage is too small. The disease involves multiple organ tissues, mainly liver, kidney, heart and muscle, most of which are characterized by hypoglycemia. The disease is divided into two major categories: liver-hypoglycemic glycogen storage disease and muscle-energy disorder glycogen storage disease. class. basic knowledge The proportion of illness: 0.005%-0.007% Susceptible people: no specific population Mode of infection: non-infectious Complications: liver fibrosis muscle atrophy ascites

Causes of glycogen storage disease

(1) Causes of the disease

Glycogen storage disease is autosomal recessive, while phosphorylase kinase deficiency is X-linked inheritance.

(two) pathogenesis

The glycogen storage disease is a disorder of hereditary glycogen metabolism.

The synthesis and decomposition of glycogen in the body is carried out under the catalysis of a series of enzymes. When these enzymes are lacking, glycogen is difficult to be normally decomposed and synthesized, involving liver, kidney, heart, muscle and even various organs of the body. , hypoglycemia, muscle weakness, heart failure, etc., Table 1 shows the defective enzyme.

Glycogen storage disease prevention

The glycogen storage disease is a disorder of hereditary glycogen metabolism, and there is no clear relevant prevention data. The incidence rate is 1/2 million. It can be divided into 12 types depending on the difference in its enzyme deficiency (mostly catabolic defects). Except for the lack of phosphorylase kinase, they are all autosomal recessive diseases. More patients than infants and young children died.

Treatment is mainly to delay the development of the disease, increase muscle strength, improve symptoms and improve respiratory suffering, prolong life, improve quality of life, and alleviate pain.

Glycogen storage disease complications Complications liver fibrosis muscle atrophy ascites

Liver fibrosis, muscle atrophy, abdominal varices, cirrhotic portal hypertension, ascites and esophageal varices.

Symptoms of glycogen storage disease common symptoms muscle atrophy liver fibrosis renal failure glomerular sclerosis hepatic enlargement coma convulsion

Glycogen storage disease mainly manifests as hepatomegaly and hypoglycemia, including type Ia (glucose-6-phosphatase deficiency) and rarer type Ib (G-6-P microsomal transferase deficiency), type III, type VI And the X-chromosome and autosomal recessive phosphatase b-kinase deficiency, muscle-energy disorder glycogen storage disease mainly manifests as muscle atrophy, hypotonia, dyskinesia, including V-type, VII-type, glycerol phosphate Lack of enzyme and lack of LDHM subunit, and other type II, type IV and so on.

1. Type I glycogen storage disease: The most common clinical, due to the lack of glucose-6-phosphatase, can not hydrolyze glucose 6-phosphate to glucose, the main performance:

(1) fasting induces severe hypoglycemia, the child appears hypoglycemia after birth, convulsions and even coma, long-term hypoglycemia affects brain cell development, mental retardation, death within 2 years of age.

(2) Acetosterone and lactic acidosis.

(3) hyperlipidemia, hip and limbs have yellow tumors, centripetal obesity, abdominal distension, body shape is "doll".

(4) Hyperuricemia.

(5) A large amount of glycogen deposition in hepatocytes and renal tubular epithelial cells, liver enlargement in the neonatal period, enlargement of the kidney, when growing into an adult, single or multiple hepatic adenomas may occur, progressive glomerulosclerosis, Renal Failure.

(6) Growth retardation, forming a dwarf state.

2. Type II glycogen storage disease: There are glycogen deposits in the whole body tissues, especially the myocardial glycogen infiltration and hypertrophy. The infant type is the first to occur 1 month after birth, rarely survives to 1 year old, and looks like a cretin. Disease, tongue, cough, difficulty breathing, died of cardiopulmonary failure before the age of 2, adolescent type mainly for progressive muscular dystrophy, adult type showed skeletal muscle weakness.

3. Type III glycogen storage disease: accumulation of multi-branched glycogen, also known as boundary dextrin disease, the main performance:

(1) Hypoglycemia: milder than type I.

(2) The liver is large and can develop liver fibrosis and cirrhosis.

(3) Growth delay.

4. Type IV glycogen storage disease: accumulation of less branched glycogen, also known as amyloplast disease, liver, liver cirrhosis, growth disorders, low muscle tone, such as newborn babies with cirrhosis should be excluded from the disease, children He died of heart and liver failure more than 1 year old.

5.V-type glycogen storage disease: Due to the lack of phosphorylase in the muscle, although there is a high content of glycogen in the muscles of the patient, there is little or no lactic acid in the blood after exercise, more adolescents are sick, moderate exercise can not be completed, a small amount of muscle Unrestricted activity, muscle fatigue, tendon, and myosinuria.

6. Type VI glycogen storage disease: mainly manifested as hepatomegaly, with low or no hypoglycemia.

7. Type VII glycogen storage disease: muscle pain after exercise, spasm, myosinuria, mild non-spherical erythrocyte hemolytic anemia.

8. Phosphatase b kinase deficiency (type VIII or IX) Liver, occasionally fasting hypoglycemia, growth retardation, self-remission during puberty.

9. X-type glycogen storage disease: liver, muscle glycogen deposition, liver enlargement, fasting hypoglycemia, muscle spasm, a certain degree of mental retardation.

10. O is a deficiency of glycogen synthase: patients usually have fasting hypoglycemia, high blood ketones, muscle spasms and a certain degree of mental retardation, which is easily confused with hypoglycemic ketosis.

Examination of glycogen storage disease

1. Fasting blood glucose measurement.

2. Blood total cholesterol, triglyceride determination.

3. Blood lactate determination, uric acid determination.

4. Glucagon test.

5. Determination of liver function transaminase.

According to the condition, bone X-ray examination, abdominal B-ultrasound, electrocardiogram, echocardiography, etc. should be selected, and if necessary, tissue or organ pathological biopsy should be performed.

Diagnosis and identification of glycogen storage disease

Diagnostic points

1.I type diagnosis basis

(1) Clinical manifestations: large liver, fasting hypoglycemia, short stature, obesity, etc.

(2) Blood biochemical examination: low fasting blood glucose, elevated blood triglyceride and cholesterol, elevated blood lactic acid and uric acid.

(3) Glucagon test: glucagon 0.5mg intramuscular injection, blood glucose measurement every 15 minutes, lasting 2h, normal people 10 to 20min after fasting blood glucose can increase 3 ~ 4mmol / L, the patient increased <0.1 Methyl/L, blood glucose still did not increase within 2h, lactic acid increased by 3 ~ 6mmol / L, and increased the existing lactic acidosis, blood pH decreased.

(4) Liver biopsy: It is the basis for the diagnosis of this disease. It is determined that the patient's liver glycogen often exceeds the normal value of 6%, the glucose-6-phosphatase activity is reduced or even absent, and there is a large amount of glycogen deposition in the nucleus.

(5) conversion of fructose or galactose to glucose test: rapid intravenous infusion of fructose (0.5g / kg) or galactose (1g / kg) 25% solution, blood taken every 10 minutes for 1h, blood determination Glucose, lactose, fructose, galactose content, blood glucose does not rise in patients, and lactic acid rises significantly.

(6) X-ray examination of the bone: visible osteophyte delay and osteoporosis.

2. Type II diagnosis basis

(1) Symptoms and signs: The child has poor growth and development, cardiac hypertrophy and muscle relaxation.

(2) Increased creatine phosphatase and aldolase.

(3) Diagnosis depends on muscle, liver biopsy, electron microscopy shows glycogen granule deposition, lack of 1,4-glucosidase, and skin biopsy fibroblast culture does not exist.

(4) Glycogen particles can be seen in amniocytes during early pregnancy.

3.Type III diagnosis basis

(1) Symptoms and signs: large liver, muscle weakness.

(2) Glucagon test: After an intramuscular injection of 0.5 mg in the morning, the patient's blood glucose does not rise or rise very little; after 2 hours of intramuscular injection of 0.5 mg, blood glucose can rise by 3 to 4 mmol/L, and the blood lactate concentration remains unchanged. .

(3) Liver or muscle biopsy: purple reaction with iodine determination, confirmed the existence of bound dextrin, can also be used as red blood cells, white blood cells plus iodine detection.

(4) Determination of red blood cell, leukocyte starch 1,6-glucosidase activity.

4. Type IV diagnosis according to the child with cirrhosis, hepatosplenomegaly, jaundice and ascites, liver tissue iodine test starch was purple reaction was positive.

5.V type diagnosis basis

(1) Symptoms and signs: limited muscle activity, tendon and so on.

(2) beam arm exercise test: the patient's upper arm is tied to the blood pressure belt, and the air is forced to reach the systolic blood pressure to block the blood flow, and then the patient is stretched and the finger is repeatedly exercised for 1 min. The blood lactic acid is measured before and after the exercise. Lactic acid increased after exercise, and the patient's blood lactate did not increase.

(3) Muscle biopsy showed accumulation of muscle glycogen and lack of muscle phosphorylase.

6.VI type diagnosis basis

(1) Symptoms and signs: Liver is large, and hypoglycemia may occur.

(2) Fasting or postprandial injection of glucagon does not increase blood sugar.

(3) Liver biopsy has high glycogen content, low phosphorylase activity, and low activity in leukocytes.

7. Type VII diagnosis basis

(1) Symptoms and signs: same as V type.

(2) Muscle biopsy lacks phosphofructokinase, which is low in red blood cells.

8. Diagnostic basis for phosphatase b kinase deficiency

1 symptoms and signs: such as liver, etc.

2 Determination of decreased activity of leukocytes or hepatocytes.

9.X type diagnosis basis

1 liver large;

2 glucagon test positive;

3 liver or muscle biopsy.

10.O type diagnosis basis

1 symptoms and signs;

2 glucagon test: no response in the fasting test, hyperglycemia after meal;

3 Liver biopsy liver glycogen content after meal is lower than liver wet weight 0.5%;

4 erythrocyte glycogen synthase activity assay.

Differential diagnosis

The disease should be differentiated from other metabolic disorders. The key to identification is biopsy, enzymology and chromosome examination of affected tissues or organs.

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