Introduction
Glycogen accumulation diseaseIt 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 caused by muscle tissue damage. These diseases have a common biochemical feature, that is, abnormal glycogen storage, the vast majority of glycogen storage in the liver, muscle, kidney and other tissues increased. Only a few diseases have normal glycogen storage, while glycogen has abnormal molecular structure.
Cause
Glycogen is a high molecular polysaccharide composed of glucose units, which is mainly stored in the liver and muscle as spare energy. Normal liver and muscle contain about 4% and 2% glycogen, respectively. Glucose in the human body forms uridine diphosphate glucose (UDPG) catalyzed by glucokinase, glucose phosphate mutase and uridine diphosphate glucose pyrophosphorylase. Then, the glucose molecules provided by UDPG are linked by a glycogen synthase into α-1,4-glycosidic bonds into a long chain; the glucose is transferred to 1 by the branching enzyme every 3 to 5 glucose residues. The 6-bit connection forms a branch, and if it is expanded, it eventually constitutes a macromolecule of a tree structure.
The molecular weight of glycogen is up to several million, and the outermost layer of glucose has a long linear chain, and most of them are 10 to 15 glucose units. The decomposition of glycogen is mainly catalyzed by phosphorylase, releasing glucose 1-phosphate from the glycogen molecule. However, 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 the other straight chain to ensure that the action of the phosphorylase continues.
At the same time, the debranching enzyme can release a glucose molecule linked by the α-l,6-glycosidic bond, and the repeated treatment ensures the body's demand for glucose. The α-1,4 glucosidase (acid maltase) present in lysosomes can also hydrolyze glucose chains of different lengths into oligosaccharide molecules such as maltose. GSD is caused by the lack of any enzyme in the glycogen synthesis and decomposition process, which causes the glycogen synthesis or decomposition to become disordered, resulting in the deposition of glycogen in the tissue and causing disease. Due to the different types of enzyme defects, various types of glycogen metabolism diseases are caused, and the common types are shown in the table. Among them, type I, III, VI and IX were mainly liver lesions, and type II, V and VII were mainly damaged by muscle tissue.
symptom
The disease is a hereditary disease, and 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 can occur. 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 people with this condition can't survive to adulthood, and often die 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.
diagnosis
Experimental diagnosis
1, biochemical examination of type I patients with fasting blood glucose decreased to 2.24 ~ 2.36mmol / L, lactic acid and blood glucose levels increased, blood lipid acid, uric acid value 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 for glycogen quantification and enzyme activity determination, can be used as a basis for diagnosis, but the damage is large.
5, molecular biology testing The current research is more glucose-6-phosphatase (G-6-Pase) gene, G-6-Pase deficiency can cause type I GSD. The G-6-Pase gene is located on chromosome 17, with a full length of 12.5 kb and contains five exons. A number of G-6-Pase gene mutations have been detected, most of which are found in R83C and Q347X, accounting for type I GSD. 60%. However, there are regional differences. The Chinese population has the highest detection frequency of nt327G→A (R83H), followed by nt326G→A (R83C). Therefore, CpG on the 83rd codon of G-6-Pase gene seems to be a hot spot of mutation. The PCR-binding DNA sequence analysis or ASO hybridization method can correctly identify the mutant alleles carried by 88% of type I glycogen storage patients. Genetic testing can avoid invasive tissue biopsy and can also be used for carrier detection and prenatal diagnosis.
Identification
The disease needs to be differentiated from diabetes:
Diabetic patients also have symptoms of acidosis and hypoglycemia, but 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 sub-symptoms.
complication
It can be complicated by lactateemia, acidosis, ketonuria, hyperlipidemia, infection, and serious death from acidosis or infection.
treatment
Western medicine treatment
The treatment uses a high-protein, high-glucose diet, and is fed several times to maintain normal blood sugar levels, especially at midnight to avoid hypoglycemia in the morning. Other treatments include preventing infection and correcting acidosis (NaHCO3 is available, sodium lactate is banned). If the blood lipids continue to rise after correcting hypoglycemia, 50 mg/(kg·d) of clofibrate can be used. If hyperuricemia cannot be controlled by diet therapy, 5 to 10 mg/(kg·d) of allopurinol may be used. Hormone therapy is beneficial for maintaining normal blood sugar levels and increasing appetite. Glucagon, various steroid hormones, and thyroxine may have temporary effects on improving symptoms. Surgical methods such as portal-cavity anastomosis, so that the intestinal absorption of glucose across the liver, directly into the blood circulation, may postoperative liver shrinkage, accelerated growth, but the long-term effect is not certain. There are also reports of liver transplants, the effect is unknown and difficult to promote. Others have adopted enzyme replacement therapy, but the effect is not good.
Glycogen accumulation type IV: no specific treatment of glycogen, high protein and low sugar diet, adding corn oil failed to prevent liver cirrhosis. The use of purified glucosin failed to achieve a positive effect. Aspergillus extracts can dramatically reduce hepatic glycogen and are therefore a promising treatment. In addition, liver transplantation can be performed.
In short, the main treatment of this disease is diet therapy and symptomatic treatment, so that children can survive the infants and young children, because the body gradually adapts to other metabolic pathways after 4 years old, the clinical symptoms can be alleviated.
The above content is for reference only, please consult the relevant physician or relevant medical institution if necessary.
prevention
The disease belongs to hereditary disease and cannot be cured. The treatment is mainly to delay the development of the disease and increase the muscle strength. Improve symptoms such as difficulty breathing and improve quality of life. The preventive measure that can be done now is to strictly abide by the "non-close relatives marriage" marriage law regulations, reduce the birth rate of such patients, improve people's physical fitness, and provide people's quality of life.
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