pediatric glycogen storage disease type IX
Introduction
Introduction to pediatric glycogen storage disease type IX Glycogens storage disease (GSD) is a glycogen metabolism disorder caused by a class of congenital enzyme defects. Glycogenstoragediseasetype IX (GSD-IX) is a group of different diseases caused by the lack of phosphorylase kinase and is a hereditary disease. These include X-linked hereditary liver phosphorylase kinase deficiency, autosomal inherited liver and muscle phosphorylase kinase deficiency, specific muscle phosphokinase kinase deficiency, and cardiac phosphorylase kinase deficiency. basic knowledge The proportion of sickness: 0.0001% - 0.0007% Susceptible people: children Mode of infection: non-infectious Complications: proteinuria
Cause
Pediatric glycogen storage disease type IX cause
Causes:
This type of glycogen storage disease is caused by the lack of phosphorylase kinase. Glycogen is mainly present in the form of hepatic glycogen and muscle glycogen in the body, and is linked by a large number of glucose via -1,4-glycosidic bond (straight chain) and -1,6-glycosidic bond (branched). The branched polysaccharide is present in the cytoplasm. The synthesis and differentiation of hepatic glycogen is mainly fixed in order to maintain blood glucose concentration; muscle glycogen is the main source of muscle glycolysis. The decomposition and synthesis of glycogen is catalyzed by different enzymes. Glycogen phosphorylase exists in both a and b situations. Glycogen phosphorylase b is inactive and needs to be converted to a during the reaction. The activity of glycogen phosphorylase is regulated by adrenaline when the muscles are vigorously exercised. Adrenalin increases the concentration of cAMP via a signal transduction system, activates A kinase to phosphorylate inactive glycogen phosphorylase kinase b into active glycogen phosphorylase kinase a, glycogen phosphorylase kinase a Further, the inactive glycogen phosphorylase b becomes an active glycogen phosphorylase a, promotes glycogen differentiation, and generates energy. In the liver, the regulation of glycogen phosphorylase activity is mainly regulated by glucagon. When the blood glucose concentration is reduced to a certain level, cAMP is formed by glucagon, and A kinase is activated to phosphorylate phosphorylase kinase b. Enzyme kinase a, which catalyzes the inactive phosphorylase b, changes to active phosphorylase a, which promotes the differentiation of hepatic glycogen into glucose into the blood to achieve blood glucose.
Phosphorylase kinase is a protein kinase composed of four subunits (, , , ). The impulse from the nerve center or the regulation of hormones can activate phosphorylase, which promotes the decomposition process of glycogen. The activation of phosphorylase kinase itself is carried out through a series of actions such as Ca2, adenylate cyclase, and cyclic adenosine monophosphate (cAMP)-dependent protein hormone, which is mainly regulated by glucagon. Each of the four subunits constituting the phosphorylase kinase has a coding gene located on a different chromosome, and expression in various tissues is also different. In theory, any defect in the above process can cause the glycogen decomposition to be blocked and accumulate. In fact, only phosphorylase kinase deficiency is the most important cause, which is distinguished by the organ and genetic characteristics involved in the lesion:
1. X-linked hereditary liver phosphorylase kinase deficiency: caused by a mutation in the alpha subunit coding gene located in Xp22.
2. Autosomal inherited liver and muscle phosphorylase kinase deficiency: This is due to mutations in genes encoding alpha and beta subunits on the autosome (currently only the beta subunit has been mapped to 16q12-q13).
3. Specific muscle phosphorylase kinase deficiency: This is due to a mutation in the structural gene (located in Xql2) encoding the alpha subunit in muscle tissue.
4. Heart Phosphorase Kinase Deficiency: There have been only a few reports to date that enzyme defects are limited to the myocardium.
The diagnosis of each type of phosphorylase kinase deficiency listed above must rely on the detection of enzyme activity in diseased organs. Since phosphorylase kinase has multiple isoenzymes in various tissues, the detection of enzyme activity in peripheral blood red and white blood cells may be misdiagnosed.
Pathogenesis:
It is caused by a congenital deficiency of phosphorylase kinase. Currently, it is divided into three subtypes according to hereditary type and affected tissues. IXa is an autosomal recessive inheritance; IXb is associated with recessive inheritance, male morbidity. Both of these subtypes involve the liver, skeletal muscle is unaffected, and biochemistry and morphology are normal. The IXc type is autosomal recessive, and both liver and muscle phosphorylase kinases lack activity.
Prevention
Pediatric glycogen storage disease type IX prevention
The prevention of type 1-3 of glycogen storage disease can be referred to the prevention method of glycogen storage disease. It should include prevention of infection during pregnancy, avoiding old-age births, close relatives, avoiding radiation, exposure to chemical substances, and abnormal genetic material. Preventive eugenics measures:
1. Prohibit close relatives from getting married.
2. Premarital examination to discover genetic diseases or other diseases that should not be married.
3. The detection of the carrier is determined by group census, family survey and pedigree analysis, laboratory examination and other means to determine whether it is a genetic disease, and determine the genetic mode.
4. Genetic counseling.
5. Prenatal diagnosis: prenatal diagnosis or intrauterine diagnosis is an important measure of preventive eugenics.
The prenatal diagnosis technique used includes 1 amniocyte culture and related biochemical examination (amniotic puncturing time is preferably 16 to 20 weeks of pregnancy); 2 determination of maternal blood and amniotic fluid alpha-fetoprotein; 3 ultrasound imaging (applicable in about 4 months of pregnancy) 4X line examination (after 5 months of pregnancy) is beneficial for the diagnosis of fetal skeletal deformities; 5 chromatin determination of villus cells (40 to 70 days of conception), predicting fetal gender to help diagnose X-linked genetic diseases; Application of gene linkage analysis; 7 fetaloscopy.
Through the application of the above technology, the birth of a fetus with severe genetic diseases and congenital malformations is prevented.
Complication
Pediatric glycogen storage disease type IX complications Complications
1. Myosinuria: refers to a large amount of muscle protein and myosin in the urine. Myosin itself causes direct damage to the epithelial cells of the renal tubules, and also causes vasoconstriction of the kidney itself; in addition, in the absence of fluid or acidic environment, myosin easily forms crystals in the renal tubules, and Further, the renal tubules are blocked, and thus rhabdomyolysis is likely to cause acute renal failure. Common clinical symptoms are local or systemic muscle soreness. When the kidneys are affected, oliguria occurs and the urine is darker.
2. Growth retardation: The age and gender height of children are 2 standard deviations below the median, but less than or equal to the median minus 3 standard deviations, which is moderate growth. Delayed, such as a median of less than the reference population minus 3 standard deviations for severe growth retardation.
3. Progressive muscle weakness and atrophy, heart enlargement and heart failure.
Symptom
Pediatric glycogen storage disease type IX symptoms common symptoms fasting hypoglycemia coagulopathy ketoacidosis liver swelling growth slow symmetry muscle weakness dyslipidemia lactic acid accumulation excessive intelligent decline
Glycogen storage disease type IX is a group of different diseases caused by the lack of phosphorylase kinase, due to glycogen (the storage form of sugar in the body, mainly in the presence of hepatic glycogen and muscle glycogen). Synthesis of hepatic glycogen Muscle glycogen is the main source of muscle glycolysis in order to maintain blood glucose concentration. Glycogen is composed of many glucoses via -1,4-glycosidic bonds (straight chain) and -1. A 6-glycosidic bond (branched) is a branched polysaccharide, which is present in the cytoplasm. A specially designated enzyme deficiency or deletion in the metabolism causes abnormal glycogen storage. The enzymes at different sites are shown below. Various symptoms caused by missing:
1.X-linked hereditary liver phosphorylase kinase deficiency:
A) Mechanism of action: In the liver, the regulation of glycogen phosphorylase activity is mainly regulated by glucagon. When the blood glucose concentration is reduced to a certain level, cAMP is formed by glucagon, and A kinase is activated to activate phosphorylase. Kinase b becomes phosphorylase kinase a, catalyzing the inactive phosphorylase b to be changed to active phosphorylase a, which promotes the differentiation of hepatic glycogen into glucose into the blood to achieve blood glucose.
B) Symptoms: Loss of enzyme activity in liver tissue and red and white blood cells in children, but normal in muscle cells. Most children develop growth retardation and hepatic disease at 1 to 5 years old; blood cholesterol, triglyceride and transaminase values Mild increase, normal lactic acid and uric acid, blood sugar is basically normal, ketone body can be seen when hunger, with age, blood biochemical changes and liver disease can gradually return to normal, adult height can reach normal people.
2. Autosomal hereditary liver and muscle phosphorylase kinase deficiency: severe early hepatic and growth retardation in children, some children with low muscle tone, mild acidosis or no acidosis. By the time of adolescence or adulthood, the liver can still be slightly larger and the transaminase is slightly elevated. Sometimes fasting hypoglycemia can occur, and the response to adrenaline and glucagon is normal. According to this, it can be distinguished from the GSD-VI type.
3. Specific muscle phosphorylase kinase deficiency: the child presents muscle pain and myosinuria after exercise, or manifests as progressive muscle weakness and atrophy, due to normal enzyme activity in the liver and blood cells, it is not With liver enlargement, heart and other diseases.
4. Cardiac Phosphorylase Kinase Deficiency: So far only a few reports have been published. The enzyme deficiency is limited to the myocardium. The child presents with heart enlargement and heart failure during infancy, and the disease progresses rapidly and collapses in the early years.
Examine
Examination of pediatric glycogen storage disease type IX
1. Enzyme activity assay: The diagnosis of each type of phosphorylase kinase deficiency must rely on the detection of enzyme activity in diseased organs. Since phosphorylase kinase has multiple isoenzymes in various tissues, the detection of enzyme activity in peripheral blood red and white blood cells may be misdiagnosed.
2. Blood glucose monitoring: blood cholesterol, triglyceride and transaminase values are slightly increased, lactic acid and uric acid are normal, blood sugar is basically normal, ketone body can be seen when starving, sometimes fasting hypoglycemia, adrenaline and pancreatic hyperglycemia The response of the prime is normal, and myosinuria can occur after exercise.
3. Regular X-ray, B-ultrasound, electrocardiogram and electromyography. Generally, the liver is enlarged, the heart is enlarged, and the EMG is abnormal.
Diagnosis
Diagnosis and diagnosis of pediatric glycogen storage disease type IX
Children with autosomal inherited liver and muscle phosphorylase kinase deficiency must be differentiated from GSD-VI type. The former responds normally to adrenaline and glucagon, and can be differentiated from GSD-VI. And the GSD-VI type is caused by defects in liver phosphorylase. There was no morbidity in the neonatal period or in infants and young children, and there was no significant gender difference. It is clinically similar to glycogen storage disease type I and III, but lighter than type I. Most children have liver enlargement and growth retardation in early childhood, and may have mild blood lipids and elevated transaminase. Hypoglycemia is rare.
Because the symptoms are sometimes slightly missed, it is considered to be benign liver, no symptoms of heart and skeletal muscle involvement, and normal intelligence. With age, liver enlargement and growth lag are gradually improving, and often disappear during puberty. Most children do not need treatment.
