Galactosemia | Anatomy2Medicine
Galactosemia Causes

Galactosemia

    • Metabolism of galactose
    • Conversion of galactose to intermediates of glucose pathways
      • Galactose is phosphorylated by ATP to galactose 1-phosphate
        • Enzyme is galactokinase.
      • Galactose 1-phosphate reacts with uridine diphosphate (UDP)-glucose and forms glucose 1-phosphate and UDP-galactose.
        • Enzyme is galactose 1-phosphate uridylyltransferase.
      • UDP-galactose is epimerized to UDP-glucose
        • Enzyme is UDP-glucose epimerase.
        • Reaction is readily reversible
      • In the liver, these glucose derivatives are converted to blood glucose during fasting or to glycogen after a meal.
      • In various tissues,the glucose1-phosphate forms glucose- 6 phosphate and feeds into glycolysis.
    • Other fates of UDP-galactose

 

  • UDP-galactose can be produced either from galactose or from glucose via UDP-glucose and an epimerase.

 

      • UDP-galactose supplies galactose moieties for the synthesis of glycoproteins, glycolipids, and proteoglycans

 

  • The enzyme that adds galactose units to growing polysaccharide chains is galactosyl transferase.

 

      • UDP-galactose reacts with glucose in the lactating mammary gland to produce the milk sugar lactose.
        • The modifier protein, alpha-lactalbumin
          • reacts with galactosyl transferase, lowering its Km (Michaelis constant) for glucose so that glucose adds to galactose (from UDP-galactose), forming lactose.
      • Conversion of galactose to galactitol
      • Aldose reductase reduces the aldehyde of galactose to an alcohol, forming galactitol.
    • Applied aspects :

 

  • Galactokinase deficiency

 

        • results in  galactosemia and galactosuria
        • This results in the development of cataracts in infants without appropriate dietary restriction
        • these patients are otherwise asymptomatic, unlike the more severe classic galactosemia.
      • Classic galactosemia
        • results from a deficiency of galactose 1-phosphate uridylyltransferase. The disorder typically presents with hepatomegaly, jaundice, hypoglycemia, convulsions, and lethargy.
        • The infant may have difficulty feeding, poor weight gain, and the development of cataracts
        • Infants are at increased risk for neonatal sepsis due to Escherichia coli.
        • Neonatal screening tests typically detect the disorder early
        • eliminate all dietary galactose and preventing the development of more serious complications, including mental retardation and cirrhosis
      • Deficiency of UDP-glucose epimerase occurs in two distinct forms
        • first is a benign condition
          • a deficiency in only leukocytes and erythrocytes
        • The second is more serious
          • it involves all tissues and has symptoms similar to classic galactosemia with the addition of hypotonia and nerve deafness.

 

  • Management requires the elimination of dietary galactose.

 

      • Galactitol, like sorbitol, accumulates in cells, increasing their osmotic pressure and promoting cell swelling.
        • It is this swelling that ultimately leads to damage of nerves, lens of the eye, and liver cells in the defects in galactose metabolism