glycogen storage disease
Introduction
Introduction to glycogen accumulation disease Glycogen accumulation disease is a type of glycogen metabolism disorder caused by congenital enzyme defects, most of which are autosomal recessive, and the incidence varies from race to race. According to European data, the incidence rate is 1/(20,000 to 25,000). There are at least 8 kinds of enzymes necessary for glycogen synthesis and catabolism. There are 12 types of clinical diseases caused by these enzyme defects, among which type I, III, IV, VI and IX are mainly liver lesions; II. Types V and VII are mainly damaged by muscle tissue. These diseases have a common biochemical feature, that is, abnormal glycogen storage, the vast majority of glycogen stores in the liver, muscle, kidney and other tissues increased, only a few species of glycogen storage is normal, and The molecular structure of glycogen is abnormal. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: hyperlipidemia
Cause
Cause of glycogen accumulation disease
Genetic factors (90%)
Autosomal recessive inheritance, phosphorylase kinase deficiency is X-linked inheritance. Glycogen accumulation disease is caused by the lack of enzymes required in the process of glycogen synthesis and decomposition, which causes obstacles in the synthesis or decomposition of glycogen, leading to the deposition of glycogen in tissues, causing various diseases due to different types of enzyme defects. Type of glycogen metabolism disease.
Pathogenesis
Glycogen is a high molecular polysaccharide composed of glucose units. It is mainly stored in the liver and muscle as spare energy. The normal liver and muscle contain about 4% and 2% glycogen, respectively. The glucose in the human body is in glucokinase and glucose phosphate. The uridine diphosphate glucose (UDPG) is formed by mutase and uridine diphosphate glucose pyrophosphorylase, and then the glucose molecules provided by UDPG are linked by -1,4-glycosidic bonds by glycogen synthase. A long chain, every 3 to 5 glucose residues are transferred by branching enzymes, and the 1 and 4 linked glucose are transferred to 1,6-position to form a branch. If it is expanded, it will eventually form a macro-molecular structure of the dendrimer. The molecular weight is up to several million, and the outermost glucose has a long linear chain, mostly 10-15 glucose units. The decomposition of glycogen is mainly catalyzed by phosphorylase, releasing glucose 1-phosphate from the glycogen molecule, but The role of phosphorylase is limited to 1,4 glycosidic bonds, and when there are only 4 glucose residues before the branching point, it must be debranching enzyme (starch 1,6-glucosidase, amyol-1,6-glucosidase) Transfer three of these residues to other straight chains The action of the phosphorylase is ensured, and at the same time, the debranching enzyme can release a glucose molecule linked by the -l,6-glycosidic bond, thus repeating the operation to ensure the body's demand for glucose, which exists in the lysosome. The -1,4 glucosidase (acid maltase) can also hydrolyze glucose chains of different lengths into oligosaccharide molecules such as maltose, which is due to the lack of any enzyme in the glycogen synthesis and decomposition process. The defects cause the synthesis or decomposition of glycogen to cause obstacles, which cause the glycogen to deposit in the tissue and cause disease. Due to the different types of enzyme defects, various types of glycogen metabolism diseases are caused. The common types are shown in Table I, III, VI. Type IX is mainly liver lesions, and type II, V, and VII are mainly muscle tissue damage.
Prevention
Glycogen accumulation disease prevention
The disease belongs to hereditary disease and cannot be cured. The treatment mainly delays the development of the disease, increases muscle strength, improves symptoms such as dyspnea, and improves the quality of life. The preventive measure that can be done now is to strictly abide by the "non-close relative marriage" marriage law. Regulations to reduce the birth rate of children with this disease, improve people's physical fitness and provide people with a quality of life.
Genetic counseling
Genetic counseling for family history can help affected adults to have selective fertility.
Premarital examination: including a detailed inquiry about the medical history and treatment of both men and women and their family members, especially the presence or absence of congenital malformations, genetic history and close relatives. Family surveys, blood test chromosomal tests, or genetic tests should be performed to detect carriers.
Prenatal consultation: pregnant women: medication during pregnancy should be guided by a doctor. Do a good job prenatal checkup. The patient must have a prenatal diagnosis for the child. Puncture amniocente in pregnancy to check:
1 Increased mucopolysaccharides were found in amniotic fluid (but not diagnostically until 16 weeks of gestation).
2 After amniocentesis, the cells can be analyzed for early diagnosis, so that the pregnancy can be terminated early.
Complication
Glycogen accumulation disease complications Complications
It can be complicated by lactateemia, acidosis, ketonuria, hyperlipidemia, infection, and serious death from acidosis or infection.
Symptom
Symptoms of glycogen accumulation disease Common symptoms Ketoacidosis Liver enlargement Slow growth Powerless liver and hard hypoglycemia
The disease is a hereditary disease. The child has a liver enlargement at birth. With age, there are obvious symptoms of hypoglycemia, such as weakness, sweating, vomiting, convulsions and coma, and ketoacidosis. The child has growth retardation, intellectual barrier-free, short stature, obesity, pale yellow skin, abdominal bulging, markedly enlarged liver, hard texture, poor muscle development, weakness, especially the lower limbs, most of the patients can not survive In adulthood, he often dies from acidosis and coma. Mild cases can be improved in adulthood. At present, the disease can be divided into more than a dozen subtypes, of which type I is the most common.
Examine
Examination of glycogen accumulation disease
1. Biochemical examination: The fasting blood glucose of type I patients was reduced to 2.24~2.36mmol/L, the content of lactic acid and blood glucose was increased, and the value of lipioic acid and uric acid was increased.
2, determination of leukocyte enzymes: may be helpful for patients with type III, IV, VI, IX.
3. Sugar metabolism function test
(1) Adrenaline tolerance test After 60 minutes of injection of adrenaline, blood glucose levels were not increased in patients with type 0, I, III or XII.
(2) Glucagon test 0, I, III, IV patients showed low blood glucose response, repeated 1 to 2 hours after the meal, O, III blood sugar can be converted to normal.
(3) Fructose or galactose changed to glucose test Type I patients did not increase glucose when loading fructose or galactose, but lactic acid increased significantly.
(4) The glucose tolerance test exhibited typical diabetes characteristics.
4, muscle tissue or liver tissue biopsy: biopsy tissue for glycogen quantification and enzyme activity determination, can be used as a basis for diagnosis, but the damage is large.
5, molecular biology test: the current study is more glucose-6-phosphatase (G-6-Pase) gene, G-6-Pase deficiency can cause type I GSD, G-6-Pase gene is located in the 17th Chromosome, full length 12.5Kb, contains 5 exons, and has detected a variety of G-6-Pase gene mutations, most of which are found in R83C and Q347X, accounting for about 60% of type I GSD, but there are regional differences, China The highest frequency of nt327GA(R83H) was detected by nt327GA(R83H), followed by nt326GA(R83C). Therefore, CpG on the 83rd codon of G-6-Pase gene seems to be a hot spot of mutation, using PCR-binding DNA sequence analysis or ASO. The hybridization method can be correctly identified. Mutational alleles carried by 88% of patients with type I glycogen accumulation syndrome, genetic testing can avoid invasive tissue biopsy, and can also be used for carrier detection and prenatal diagnosis.
Diagnosis
Diagnosis and identification of glycogen accumulation disease
The disease needs to be differentiated from diabetes:
Diabetes is a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion and/or impaired insulin action. Sustained hyperglycemia and long-term metabolic disorders can lead to damage to the tissues and organs of the body, especially the eyes, kidneys, cardiovascular and nervous system, as well as dysfunction and failure. Severe cases can cause acute complications such as dehydration, electrolyte imbalance and acid-base balance disorders, ketoacidosis and hyperosmolar coma. However, the typical symptoms of diabetic patients are three more and one less, that is, polydipsia, polyuria, polyphagia and weight loss, which can be identified according to the secondary symptoms.
