Introduction
Galactose is a type of carbohydrate also known as monosaccharide (single compound type) sugar. In simple terms, it is also known as milk sugar. It is about 65 % as sweet as sucrose and glucose. A lactose molecule is a disaccharide molecule made up of a glucose molecule and a galactose molecule when combined in atomic form. Milk and milk-containing products that contain lactose are the main dietary sources of galactose. In the intestine, lactose is hydrolyzed (breaks down) to its monosaccharides, glucose, and galactose. The liver, the primary site for galactose metabolism, is where lactose is absorbed, metabolized, and utilized in the body.
How Does Galactose Metabolism Take Place?
Galactose metabolism occurs through three sequential steps that are required for galactose metabolism. A pathway of conversion of galactose and uridine diphosphoglucose to glucose-1-phosphate and uridine diphosphogalactose occurs through three sequential enzymes involved known:
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Galactokinase (GALK, EC 2.7.1.6).
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Galactose-1-phosphate uridylyltransferase (GALT, EC 2.7.7.12).
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Uridine phosphogalactose 4-epimerase (GALE, EC 5.1.3.2).
What Are Galactose Metabolism Defects?
In galactose metabolism defects, galactose and its metabolic byproducts are excreted in excess, and the activities of the enzymes involved in galactose metabolism uridine diphosphoglucose (UDP-glucose) and uridine diphosphogalactose (UDP-galactose) are deficient as a result of inborn errors of galactose metabolism. Classical galactosemia, which affects between one in 10,000 and one in 30,000 live births, is the most prevalent and severe of these diseases and is brought on by a GALT enzyme deficiency (galactose-1-phosphate uridylyltransferase). The least common of the three diseases is GALE deficiency.
Galactokinase (GALK, EC 2.7.1.6) Deficiency - A galactose-specific kinase (GALK) is an enzyme that converts galactose into galactose-1-phosphate in the first step of galactose metabolism. The most common clinical manifestation of GALK deficiency is bilateral cataracts, which appear shortly after birth. Such deficiency occurs due to deletions, insertions, missense, and nonsense mutations in molecular changes in the GALK gene.
Galactose-1-Phosphate Uridylyltransferase (GALT, EC 2.7.7.12) Deficiency - In galactose metabolism, galactose-1-phosphate uridylyltransferase (GALT) helps in the conversion of galactose-1-phosphate (Gal-1-P) and UDP-glucose into glucose-1-phosphate (Glu1-P) and UDP-galactose in the second catalytic step of galactose metabolism. Just after birth, babies with GALT deficiency develop classical galactosemia with the following symptoms:
- Jaundice.
- Liver failure.
- Hypotonia.
- Poor feeding.
- Failure to gain weight.
- Renal tubular insufficiency.
- Cataracts.
- Sepsis.
Uridine Phosphogalactose 4-Epimerase (GALE, EC 5.1.3.2) Deficiency - The final step in this galactose metabolic pathway ensures proper UDPglucose levels and UDP-galactose concentrations via UDPgalactose-4-epimerase (GALE). UDP-glucose is required for the synthesis of both GALT and glycogen. In mentally disabled patients, GALE deficiency is either asymptomatic or diagnosed later. However, severe forms of this disease may present similarly to classical galactosemia.
How Is Galactose Metabolism Deficiency Diagnosed?
Diagnosis During Pregnancy - If the mutation is known in a family, a prenatal diagnosis can be made using DNA (deoxyribonucleic acid) extracted from a chorionic villus biopsy taken around 11 weeks gestation. Prenatal testing can also be accomplished by measuring GALT enzyme activity directly in the following.
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Chorionic villus cells.
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Cultured chorionic villus cells.
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Cultured amniotic fluid cells.
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Amniotic fluid galactitol.
Galactokinase (GALK, EC 2.7.1.6) Deficiency
Galactitol toxicity has been linked to the development of cataracts and localized brain swelling. Therefore, these patients have the following analysis on diagnosis:
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Elevated plasma galactose.
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Normal to reduced red blood cell galactose-1-phosphate concentrations.
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Elevated urine galactose.
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Elevated urinary galactitol and galactonic acid.
Galactose-1-Phosphate Uridylyltransferase (GALT, EC 2.7.7.12) Deficiency
Complete molecular genetic testing for GALT deficiency is done to diagnose this condition. Complete gene sequencing is performed if there is clinical and biochemical suspicion for GALT deficiency. If this galactose deficiency is not treated, it can lead to sepsis caused by E. coli, making diagnosis difficult, and these symptoms can progress to hypotension and death.
The biochemical test of these patients includes five percent GALT enzyme activity with the following analysis:
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Elevated plasma galactose.
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Elevated urine galactose concentrations.
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Elevated Gal-1-P levels.
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Elevated urinary galactitol and galactonic acid levels.
Uridine Phosphogalactose 4-Epimerase (GALE, EC 5.1.3.2) Deficiency
Nuclear Magnetic Resonance Spectroscopy - It is a recent isotope detection method used to detect galactitol and galactonic acids. Galactitol, an osmotic regulator in the brain and lens fiber, causes swelling when it accumulates in excess in the cell. Galactitol accumulates in tissues and fluids and can be quantified in urine and amniotic fluid because it is not a substrate for the second reaction. GALE deficiency is characterized by the following:
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Elevated galactose.
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Elevated Gal-1-P.
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Elevated galactitol and galactonic acid levels.
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Normal GALT activity.
What Is the Treatment for Galactose Metabolism Defects?
Newborn
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The newborn with classical galactosemia is treated by removing all lactose from the diet.
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Breastfeeding or milk-based formulas must be discontinued when the disorder is clinically suspected, after a positive newborn screening result, and before confirmatory diagnostic tests are available.
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Most newborns are switched to a soy-based formula, though an elemental formula may also be used.
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Some infants are critically ill at the time of diagnosis and require extensive supportive care, including coagulopathy (bleeding disorder) and septicemia management.
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When a lactose-free diet is started early enough, symptoms fade quickly, jaundice resolves within days, cataracts may clear, liver and kidney functions return to normal, and liver cirrhosis can be avoided.
Children and Infants
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During weaning, parents must learn to identify all other sources of lactose and rely on the pediatrician and dietitian, who must follow published recommendations.
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Some Swiss cheeses and other hardened cheeses are free of galactose and lactose because the fermenting microorganisms clear these sugars.
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Although soy-based infant formulas normally provide adequate calcium in infancy, calcium supplementation is required at weaning.
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A completely galactose-free diet is impossible, even with strict adherence to dietary treatment.
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Galactose can be found in various vegetables, fruits, and legumes (beans, peas, lentils) as a component of galactolipids and glycoproteins, the disaccharide metabolite that can be beneficial.
Older Kids and Adults
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The galactose restriction should be kept indefinitely.
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L lactose consumption may result in cataracts, liver disease, and organic brain disease with psychiatric manifestations in children and adults.
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Milligrams of galactose cause a significant increase in galactose-1-phosphate in erythrocytes; similar increases may occur in sensitive tissues such as the brain, liver, and kidney.
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However, toxic tissue levels of galactose-1-phosphate cannot be defined, making it impossible to determine safe dietary galactose amounts.
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Patients with a high alternate metabolic pathway activity should be more tolerant of galactose.
Conclusion
Lactose must be avoided in the diet of newborns at risk of the severe form of galactose deficiency. It is unknown whether infants with this disorder require a small amount of exogenous galactose. Therefore, it is important to measure galactose levels in plasma and urine on a normal galactose intake and monitor psychomotor progress. Before diagnostic confirmation, implement a galactose-free diet immediately after an abnormally low level of galactose is found.
