galactosemia in children
Introduction
Introduction to galactosemia in children Galactose-1-phosphateuridyltransferase (Gal-1-PUT) is a congenital metabolic disorder caused by galactose-1-phosphateuridyltransferase (Gal-1-PUT) deficiency. The congenital defects of these three enzymes (kinase, transferase and isomerase) in galactose catabolism have been clinically discovered, among which galactose-1-phosphate uridine transferase deficiency is more common. basic knowledge The proportion of illness: 0.0016% Susceptible people: infants and young children Mode of infection: non-infectious Complications: jaundice, cirrhosis, ascites
Cause
Causes of galactosemia in children
(1) Causes of the disease
The disease is an autosomal recessive disorder. The lack of Gal-1-PUT in erythrocytes and hepatocytes causes obstruction of the conversion of galactose-1-phosphate to glucose-1-phosphate, resulting in galactose and galactose-1- Phosphoric acid accumulates in the bloodstream and tissues.
(two) pathogenesis
Pathogenesis
The coding gene for galactose-1-phosphate uridine acyltransferase (GLAT) is located at 9p13 to p21, and its defect is galactitol, which leads to the metabolism of galactose, galactose-1-phosphate and galactose. Accumulation in tissues, 1-galactose galactose is cytotoxic, inhibiting various enzymes in the glucose metabolism pathway, especially after the action of glucose phosphate mutase is inhibited, the glucose 1-phosphate phosphate cannot be converted into 6- Glucose phosphate blocks the decomposition process of glycogen; high concentration of galactose-1-phosphate also inhibits the gluconeogenesis process, so it presents clinical symptoms of hypoglycemia. When galactose enters the crystal, it is replaced by aldose reductase. Reduction to galactitol, deposition in the crystal causes increased osmotic pressure in the crystal, increased water content, decreased amino acid transport and decreased protein synthesis, and eventually forms a cataract. The liver, kidney, brain and other tissues of this type of child are There are a large number of 1-galactosamine and galactitol stores. These abnormal metabolites change the osmolal concentration of tissue cells and their energy metabolism, resulting in impaired function of these organs. It is not fully understood.
2. Pathological changes
Accumulation of galactose-1-phosphate can cause significant liver lesions. Early children can have diffuse hepatic steatosis and cholestasis within a few weeks after birth. As the disease progresses, hepatocytes appear as acinus after several weeks. Arrangement, bile duct proliferation in the portal area, fibrosis and cirrhosis change after 4 to 6 months, high concentration of galactose is converted into galactitol in the crystal to cause crystal cataract formation; galactose-1-phosphate in The accumulation of brain and renal tubules in development can lead to mental retardation and tubular regurgitation, and pathological changes in other tissues such as brain and kidney are lighter.
Prevention
Pediatric galactosemia prevention
The pathogenesis is not fully understood, and preventive measures are carried out in relation to hereditary diseases.
Since it has been proven that the skin fibroblasts of the diseased child have Gal-1-PUT enzyme abnormality, the enzyme analysis of the cultured amniotic fluid cells shows that the Gal-1-PUT activity is reduced, and prenatal diagnosis can be made, and Nadler et al. have used this method for production. Pre-diagnosis, but because there are simple and easy screening methods for newborns, and if the diet can be detected and controlled early, the sick children can develop normally, so it is still controversial whether prenatal diagnosis should be done.
Patients limit the intake of milk and dairy products during pregnancy, which can both reduce the mother's condition and prevent congenital cataracts in infants.
Complication
Pediatric galactosemia complications Complications jaundice cirrhosis ascites
Astragalus and liver enlargement, cirrhosis, ascites, liver failure, hemorrhage, Escherichia coli sepsis, growth retardation, intelligent development and so on.
Symptom
Symptoms of galactosemia in children Common symptoms Galactosemia sepsis jaundice ascites refusal liver enlargement liver failure weight loss sleepiness congenital lactose intolerance
Typical cases occur in the perinatal period, often vomiting, refusal to eat, weight loss and lethargy, and then jaundice and liver enlargement, and continue to feed the milk if not diagnosed in a few days after feeding the milk. Will lead to further deterioration of the disease, as early as 2 to 5 weeks of ascites, liver failure, bleeding and other end-stage symptoms, such as the use of slit lamp examination, crystal cataract formation can be found in the early stage of the disease, about 30% to 50% of children In the first week of the disease, Escherichia coli sepsis was complicated, and the condition was more serious. Most of the children who were not diagnosed and treated in time died in the neonatal period. The symptoms of a few children were mild, only after eating milk. Mild gastrointestinal symptoms, but if you continue to use dairy foods, there will be signs of growth retardation, mental retardation, cirrhosis and cataract in young infants.
Examine
Examination of galactosemia in children
Early correct diagnosis relies on laboratory testing.
1. Neonatal screening
Group screening of newborns not only achieves early diagnosis and treatment, but also provides information for genetic counseling and family planning. Most screening centers use two methods:
(1) Beutler test: The galactose-1-phosphate urinyl transferase activity for detecting blood droplet papers has the disadvantage that the false positive rate is too high.
(2) Paigen test: a semi-quantitative method for detecting galactose and galactose-1-phosphate on blood droplets. The advantage is that there are few false positives, and all three enzyme defects can be detected. Screening with the instrument (tandem MS) is especially convenient and correct.
2. Determination of reducing sugar in urine
For children with suspected symptoms, they must check whether the urine contains reducing sugar, and there may be more types of reducing sugars in the urine, such as glucose, galactose, lactose, fructose and pentose, so it is positive in qualitative test. When it is used, it should be further identified by filter paper or thin layer chromatography.
3. Enzymological diagnosis
Peripheral blood red, white blood cells, skin fibroblasts, or liver biopsy tissue can be used for the determination of enzyme activity, the most convenient for red blood cells, the enzyme activity of children with homozygous disease is absent or low; the enzyme of heterozygous carriers The activity is 50% of normal people. In recent years, various variants of the disease have been discovered by studying the characteristics of enzyme defects (Table 1). Among them, Duarte type is the most common, and the homozygous Duarte type enzyme activity is The normal 50%, heterozygous Duarte type is up to 75%, because the clinical symptoms are not present, it can only be found through group screening, "Negro" type red blood cells lack transferase activity, but its liver, intestine Some tissues still have some enzyme activity, so the clinical is also asymptomatic.
4. Other
Liver function, blood coagulation mechanism, blood sugar, blood electrolytes and blood, urine culture and other items should be tested for diagnosis if necessary.
Regular X-ray, B-ultrasound, etc., can be found in liver enlargement, cirrhosis, splenomegaly, ascites, etc., slit lamp examination, cataract can be found, can also find fundus lesions, such as retinal detachment, intraocular hemorrhage, etc., EEG Check for abnormal waveforms.
Diagnosis
Diagnosis and diagnosis of galactosemia in children
Diagnosis is mainly based on clinical symptoms and related enzyme activity determination, urinary glucose levels are normal and Ban test positive should be suspected of galactosemia, combined with erythrocyte galactose metabolism enzyme deficiency can usually be diagnosed, if the prenatal suspected fetus may have Galactosemia, prenatal diagnosis by amniocentesis, or umbilical cord blood at birth to check the enzyme activity in red blood cells. It is worth noting that amniocentesis does not understand whether the fetal brain development has been damaged, born In neonates within the next 2 months, the diagnosis of galactosemia should exclude the possibility of transient neonatal galactosemia, which is due to the fact that liver function is not fully mature. Lactose is mildly elevated, blood alpha-fetoprotein (AFP) is elevated, and it can automatically return to normal after several months. There is no galactitol and galacturic acid in the urine of children, which can be differentiated from galactosemia.
If the concentration of galactose in pregnant women is elevated, the presence of galactose-1-phosphate uridine transferase deficiency can cause damage to the fetus, including permanent mental retardation.
Because of the common jaundice, and can occur very early, should pay attention to the identification of neonatal hemolytic disease.
