Introduction
Galactosemia(galactosemia) is a toxic clinical metabolic syndrome with increased blood galactose. There are three related enzymes in galactose metabolism: congenital defects can cause galactosemia: 1 galactose-1-phosphate uridine acyltransferase (Gal-1-PUT) defect: this is a classic Galactosemia, more common; 2 galactosidase deficiency: less common; 3 urinary-galactosamine galactose-4-epimerase (UDP-Gal-4-E) deficiency: rare. Galactosemia is an inherited metabolic disease of autosomal recessive inheritance. In heterozygotes, the three related enzyme activities of galactose metabolism are about 1/2 of that of normal people, while those of homozygotes are significantly reduced. . The locus controlling the above three enzymes has been clarified. The uridine acyltransferase is on the short arm of chromosome 9, the galactose kinase is on the long arm of chromosome 17, and the galactose-epi isomerase is on chromosome 1. .
Cause
(1) Causes of the disease
Classical galactosemia occurs in the second step of galactose metabolism, in which 1-phospho-galactosidase is deficient, resulting in an autosome that is caused by the accumulation of its precursor 1-phosphate-galactose. Recessive genetic disease. Liver, kidney, crystal and brain tissue are the main affected organs.
(two) pathogenesis
The metabolism of galactose is mainly carried out in the liver, and the process is as shown below.
Defects in any of the enzymes required for galactose metabolism can lead to metabolic disorders of galactose, which directly cause an increase in the concentration of galactose and galactose-1-phosphate in the blood. Among them, galactosemia caused by galactose-1-phosphate uridine transferase (GALT) deficiency is the most common.
The galactose-1-phosphate uridine transferase deficiency is caused by gene mutation and is autosomal recessive. The gene for galactose-1-phosphate uridine transferase is located in the p13 region of the short arm of chromosome 9, and the frequency of the gene in the population is 1/150. The patients are all homozygous, and heterozygotes are generally not affected. The patient's parents can be homozygous or heterozygous, heterozygous?a href=”http://jb.jb39.com/keshi/pifu/pifubing/490b3.html ” class=blue>痈改肝虏』虻Male sputum 樘? 1-phosphate uridine transferase activity is only 50% of normal people. The galactose-1-phosphate uridine transferase deficiency in the body is mainly caused by a point mutation of GALT. Dozens of mutation sites have been found, and the concentration of galactose-1-phosphate in the blood is significantly increased due to the decrease in enzyme activity. Excessive galactose-1-phosphate is accumulated in tissues such as brain, liver and renal tubules, which can interfere with normal metabolism and cause organ damage. Further, galactose-1-phosphate can also inhibit the activities of phosphoglucose mutase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, etc., and prevent glycogen from decomposing into glucose, thereby causing hypoglycemia. An increase in galactose-1-phosphate leads to a hindrance of the normal metabolism of galactose, causing an increase in the concentration of galactose in the blood. The metabolic compensation of galactose bypass is enhanced, and the production of galactitol is also increased. Galactitol deposition in the crystal causes cataracts to occur.
In addition to the lack of galactose-1-phosphate uridine transferase, galactose kinase and uridine galactose-4-dipeptide deficiency are also galactosemia. Both are due to defects in the gene and are autosomal recessive. The galactose kinase gene is located on chromosome 17q21-22. Foreign survey data show that the frequency of neonatal heterozygotes is 1/107, and the homozygous frequency is 1/4 million. The lack of galactose kinase directly causes an increase in galactose in the body, resulting in increased metabolism of galactose bypass and increased production of galactitol. The gene for uridine diphosphate galactose-4-differase is located on chromosome 1p35-36. The deficiency of uridine galactose-4-dipeptide to diphosphate mainly leads to an increase in galactose and galactitol in vivo by affecting the metabolism of galactose-1-phosphate.
symptom
There are many regional variants of galactose-1-phosphate uridine acyltransferase, and the activity of the enzyme is affected to varying degrees. The enzyme protein molecules show different swimming speeds in electrophoresis, which contributes to the identification of the type. The currently known variants are: 1 Duarte variant; 2 black variant; 3 Indiana variant; 4 Rennes variant; 5 Bern variant; 6 Chicago variant; 7Los Angel variant.
There are fewer variants of galactose kinase, including: 1 Philadelphia variant; 2 Urbino variant; 3 partial transient galactose kinase deficiency. Uridine diphosphate galactose-4-isomerase is extremely rare. The clinical manifestations of galactosemia vary greatly depending on the type of disease and the course of the disease. Lighter patients may have no clinical symptoms, and the most severe cases are fulminant.
1. Acute disease Most children have galactose in lactation or artificial feeding of cow's milk for several days after birth, such as refusal, vomiting, nausea, diarrhea, weight loss, hepatomegaly, jaundice, bloating, hypoglycemia, proteinuria Etc. Those who have the above manifestations should consider the possibility of galactosemia. They need to carry out relevant laboratory tests. If they can be detected and taken in time, cataracts and mental retardation can occur rapidly.
2. There are no acute symptoms in the mild course, but dysphonia, cataract, mental retardation and cirrhosis gradually appear with age.
3. Others such as pseudo-cerebral tumors, for a rare manifestation, this system of galactose accumulation in the brain, followed by conversion to galactitol sputum caused by cerebral edema and increased intracranial pressure.
The diagnosis is mainly based on clinical symptoms and related enzyme activity determination. Normal urinary glucose levels and positive Ban test should be suspected to be galactosemia, combined with erythrocyte galactose metabolism enzyme deficiency can usually be diagnosed. If prenatal suspicion that the fetus may have galactosemia, prenatal diagnosis can be performed by amniocentesis, or cord blood can be taken at birth to check the enzyme activity in the red blood cells. It is worth noting that amniocentesis does not understand whether fetal brain development has been compromised. In neonates within 2 months after birth, 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, and is characterized by blood. Mild galactose is 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.
diagnosis
Note that the identification of infantile hepatitis syndrome, infantile hepatitis syndrome liver function damage is obvious, jaundice is mainly caused by elevated direct bilirubin.
complication
Childhood can have neurological deafness. A small number of patients may have retinal and vitreous hemorrhage, jaundice and hepatic enlargement, cirrhosis, ascites, liver failure, hemorrhage, Escherichia coli sepsis, growth retardation, intelligent development, high chloride acidosis, proteinuria, Amino acid urine and hypoglycemia.
treatment
(a) treatment
1. Limit the milk to stop using milk immediately, switch to soy milk, rice flour, etc., supplemented with vitamins, fats and other nutritive essential substances. Although soy milk contains raffinose and stachyose which can decompose galactose, it cannot be absorbed by the human intestine, so it is not harmful to treatment. Clinical symptoms are usually improved after 3 to 4 days of limiting milk, and liver function improves after 1 week.
After the child begins to feed on supplementary foods, all foods that may contain milk and certain fruits and vegetables containing lactose such as watermelons and tomatoes must be avoided.
2. Support treatment of intravenous glucose, fresh plasma, pay attention to supplement electrolytes.
3. Antibiotics should be given appropriate antibiotics for children with sepsis and given active supportive care.
(two) prognosis
The prognosis of a child depends on the availability of early diagnosis and treatment. Most people who have not been treated correctly die in the neonatal period, and the average life expectancy is about 6 weeks. Even if they are spared, they will leave behind mental retardation. Most of the children diagnosed with early diagnosis have normal growth and development, but most of them may have problems such as learning disabilities, language difficulties or behavioral abnormalities in adulthood. Female children have almost hypogonadism after the elderly, the reason is not clear.
The earlier the start of diet control, the better the prognosis of the child. Although the child's IQ can be within the normal range, the academic performance is still not comparable to normal children. Since the deficiency of galactose-metabolizing enzymes in children does not gradually improve with age, diet control is required for life. Those who cannot adhere to diet control can experience varying degrees of mental retardation, growth disorders, and cataracts.
prevention
Early detection and dietary treatment of galactosemia can slow the occurrence of cataracts. Therefore, this disease is an indication for screening for neonatal diseases. The main measure of prevention is the removal of lactose and other galactose-containing substances from food.
All three types are autosomal recessive. High-risk pregnant women should limit lactose and other galactose-containing substances in food to reduce damage to the fetus.
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