OVERVIEW
Galactosemia is a toxic clinical metabolic syndrome characterized by elevated blood galactose. Inborn defects in any of the three enzymes involved in galactose metabolism can lead to galactosemia.
Galactosemia is an autosomal recessive inborn metabolic disorder. In heterozygotes, the activity of the three enzymes involved in galactose metabolism is about 1/2 that of normal individuals, whereas in heterozygotes, the enzyme activity is significantly lower. The loci controlling the three enzymes are now well characterized, with uridyltransferase on the short arm of chromosome 9, galactokinase on the long arm of chromosome 17, and galactose-epimerase on chromosome 1.
Etiology
Classic galactosemia occurs as an autosomal recessive disorder caused by a deficiency of 1-phospho-galactose uridyltransferase, the second step in galactose metabolism, leading to accumulation of its precursor 1-phospho-galactose. The liver, kidneys, crystals and brain tissue are the main organs involved.
Symptoms
There are many regional variants of galactose-1-phosphate uridyltransferase, with varying degrees of involvement of the enzyme’s activity, and the enzyme protein molecules show different speeds on electrophoresis, which aids in the identification of types. There are fewer variants of galactokinase. The clinical manifestations of galactosemia vary greatly depending on the type and duration of the disease, with the mild cases showing no clinical symptoms and the most severe cases showing a fulminant form.
1. Acute course
Most of the children are born with galactosemia a few days after birth, due to breastfeeding or artificial feeding of cow’s milk containing galactose, there are refusal of breastfeeding, vomiting, nausea, diarrhea, weight loss, hepatomegaly, jaundice, abdominal distension, hypoglycemia, proteinuria and so on. Those who have the above mentioned manifestations should be considered to have galactosemia, and need to carry out the relevant laboratory tests immediately, and if they can be detected in a timely manner, and to take the appropriate measures, otherwise cataract and mental developmental disorders may appear rapidly.
2. Mild course
Most of the cases do not have acute symptoms, but with ageing, dysarthria, cataract, mental retardation and cirrhosis gradually appear.
3. Other
Pseudotumor cerebri is a rare manifestation, which is due to the accumulation of galactose in the brain, and then transformed into galactitol, resulting in cerebral edema and increased cranial pressure.
Examination
1. Laboratory examination
(1) Urine galactose test: urine sugar is positive, glucose oxidase method is negative, paper chromatography can identify it as galactose.
(2) Newborn screening for galactosemia The Beutler method is used to screen for defective enzymes and to observe the presence or absence of fluorescence, which is used as the basis for the final evaluation, and there is no fluorescence in this disease. Defects in enzyme activity can also be seen in the liver, intestinal mucosa, fibroblasts and leukocytes.
(3) Measurement of blood galactose concentration The normal concentration is 110-194 μmol/L (galactose oxidase or galactose dehydrogenase method is applied), which is elevated in patients.
(4) Measurement of urinary galactose and galactitol concentrations Enzymatic measurement is available.
(5) Erythrocyte 1-phosphogalactose measurement.
(6) Galactose metabolism related enzyme assay This is important for confirming the diagnosis of the disease.
(7) Non-specific biochemical parameters such as proteinuria and glucosuria.
2. Auxiliary examination
(1) Ultrasound: Ultrasound should be performed according to the clinical findings.
(2) Fetoscopy to take fetal blood for enzyme activity measurement, to determine the content of galactitol in amniotic fluid and the activity of enzymes in amniotic fluid cells. Mutation analysis of enzyme genes can be done for prenatal diagnosis of the fetus.
(3) Galactose respiration test The conversion of 13C-galactose to 13CO2 can be quantitatively measured to understand the body’s ability to oxidize galactose.
Diagnosis
Diagnosis is confirmed mainly on the basis of clinical symptoms and related enzyme activity measurements. A positive Ban’s test with normal urinary glucose levels should raise suspicion of galactosemia, which is usually confirmed when combined with a deficiency of galactose-metabolizing enzymes in the erythrocytes. If there is prenatal suspicion that the fetus may have galactosemia, the diagnosis can be made prenatally by amniocentesis or by taking umbilical cord blood at birth to check for enzyme activity in the red blood cells.
If the maternal blood galactose concentration is elevated, with or without galactose-1-phosphate uridyltransferase deficiency, fetal damage, including permanent mental retardation, can occur.
Differential Diagnosis
Note the differentiation from infantile hepatitis syndrome, in which hepatic impairment is evident and jaundice is dominated by elevated direct bilirubin.
Complications
Neurologic deafness may be present in childhood. In a few patients, retinal and vitreous hemorrhage, jaundice and hepatomegaly, cirrhosis, abdominal effusion, hepatic failure, hemorrhage, complication of Escherichia coli septicemia, growth retardation, retardation of intellectual development, hyperchloremic acidosis, proteinuria, amino aciduria and hypoglycemia may occur.
Treatment
1. Intravenous infusion of glucose, fresh plasma, pay attention to replenish electrolytes.
2. Antibiotics
Appropriate antibiotics should be used for children with combined sepsis, and active supportive therapy should be given.
Prognosis
The prognosis of the child depends on early diagnosis and treatment. Most untreated children die in the neonatal period, with an average life expectancy of about 6 weeks, and even if they are spared, they may suffer from mental retardation later in life. Children who are diagnosed early have mostly normal growth and development, but most have learning disabilities, language difficulties, or behavioral problems in adulthood. The cause of gonadal insufficiency, which occurs in almost all female children at an older age, is not well understood.