Galactosemia

Introduction Galactose-1-phosphateuridyltransferase (Gal-1-PUT) is a congenital metabolic disorder caused by galactose-1-phosphateuridyltransferase (Gal-1-PUT) deficiency. In galactose metabolism, any one of the three related enzymes may cause galactosemia. Typically, the disease occurs during the perinatal period, and vomiting, refusal to eat, weight loss, and lethargy often occur several days after feeding the milk, followed by jaundice and liver enlargement. If you can not continue to feed the milk in time, it will lead to further deterioration of the disease, and end-stage symptoms such as ascites, liver failure, and hemorrhage occur within 2 to 5 weeks.

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.

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 may be homozygous or heterozygous, and the 1-phosphate uridine transferase activity is only 50% of normal. 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.

an examination

Related inspection

Obstetric B ultrasound

Laboratory examination

(1) Urine galactose test: urine sugar positive, glucose oxidase method urine sugar negative, paper chromatography can identify it as galactose.

(2) Neonatal screening for galactosemia: The defect enzyme was screened by the Beutler method to observe the presence or absence of fluorescence, and as a basis for the final evaluation, no fluorescence was produced in the disease. Defects in enzyme activity can also be reflected in liver, intestinal mucosa, fibroblasts, and white blood cells.

(3) Determination of blood galactose concentration: The normal concentration is 110-194 mol/L (using galactose oxidase or galactose dehydrogenase method), and the blood concentration of the patient is increased.

(4) Determination of urinary galactose and galactitol concentration: can be determined by enzymatic method.

(5) Determination of red blood cell 1-galactose.

(6) Determination of galactose metabolism related enzymes: This is an important basis for the diagnosis of this disease.

(7) Determination of non-specific biochemical indicators: such as proteinuria, glucose and urine.

2. Auxiliary inspection

(1) B-ultrasound: B-ultrasound is selected according to clinical manifestations.

(2) Determination of enzyme activity by fetal blood sampling by fetal mirror: measuring the content of galactitol in amniotic fluid and the activity of enzyme in amniotic fluid cells. A mutation analysis of the enzyme gene can be used for prenatal diagnosis of the fetus.

(3) Galactose breath test: The 13C-galactose can be quantitatively determined by conversion to 13CO2 to understand the body's ability to oxidize galactose.

Differential diagnosis

Congenital lactose intolerance: This is a disease that is different from congenital lactase deficiency and belongs to autosomal dominant inheritance. After starting feeding, there was fulminant diarrhea, acidy stool with watery vesicles, and diarrhea. Can cause vomiting, dehydration, renal tubular acidosis, disaccharide, amino aciduria, cataract, liver and brain damage, such as diagnosis can cause death. The diarrhea disappeared after stopping the feeding, and there was no lactoseuria or amino aciduria. When the lactose that has not been decomposed and absorbed enters the colon, the bacteria present in the intestine are fermented into small molecules of organic acids such as acetic acid, propionic acid, butyric acid, etc., and some gases such as methane, H2, CO2, etc. are produced, and most of these products can be Lactose reabsorbed by the colon, but not absorbed or still not decomposed can cause bowel, abdominal distension, abdominal pain, exhaust, discomfort, diarrhea and other symptoms, and some people may have hernia, nausea and so on. These symptoms are called lactose intolerance. The symptoms of lactose intolerance vary widely among individuals.

Severe lactose intolerance occurs more than 30 minutes to several hours after ingesting a certain amount of lactose. Lactose intolerance has a great impact on infants and young children, and is accompanied by diaper rash, vomiting, growth retardation, etc. Adults sometimes have nausea reactions. The number and severity of intolerance symptoms are related to a variety of factors, such as lactase activity in the small intestine, the amount of lactose ingested, and whether other foods are ingested at the same time.

Attention to the identification of infantile hepatitis syndrome, liver function damage of infant hepatitis syndrome is obvious, and jaundice is mainly caused by elevated direct bilirubin.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.