Galactose Metabolism

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Fig: Galactose Metabolism
Table Of Contents
  1. Clinical Case
  2. Importance of Galactose
  3. Galactose Metabolism
  4. Disorders-Galactosemia

Clinical Case

A male baby of 2 months age was brought to the pediatric OPD with history of one episode of seizure, yellowish discoloration of eyes for the last one month with on and off fever, poor  feeding, and excessive crying after feeds. On examination, the child appears icteric (icterus grade 3), presence of bilateral cataract and hepatomegaly noted. The laboratory investigation are as follows:

  • Fasting blood sugar: 36 mg/dl
  • Reducing sugar in urine: positive
  • Liver function: tests:
    • Total bilirubin – 20 mg/dl
    • Direct bilirubin – 6 mg/dl
    • Indirect bilirubin – 14 mg/dl
    • Total protein – 5g/dl
    •  Albumin – 3g/dl
    •  Globulin – 2g/dl
    • A/G ratio – 1.5
    • AST — 20 IU/L
    • ALT- 27 IU/L
    • ALP—200 IU/L

Importance of Galactose

Galactose is derived from disaccharide, lactose (the milk sugar) of the diet. It is important for the formation of:

• Glycolipids

• Glycoproteins

• Proteoglycans

• Lactose during lactation.

Galactose Metabolism

  • The first reaction in galactose metabolism in the liver is phosphorylation of galactose to galactose-1-phosphate, by the enzyme galactokinase, using ATP as phosphate donor.
  • Galactose-1-phosphate reacts with UDP-glucose to form UDP-galactose and glucose-1-phosphate, catalyzed by galactose-1-phosphate uridyl transferase.
  • In this reaction, galactose displaces a glucose of UDP-glucose
  • The conversion of UDP-galactose to UDP-glucose is catalyzed by a UDP-galactose-4-epimerase.
  • Finally, glucose is liberated from UDP-glucose via formation of glycogen by glycogenesis followed by Glycogenolysis

Disorders-Galactosemia

  • Galactosemia is an inborn error of galactose metabolism due to the deficiency of enzyme Galactose-1-Phosphate Uridyl Transferase (GaliPUT).
  • This enzyme is responsible for conversion of galactose-1-phosphate to glucose-1-phosphate.
  • It is an autosomal recessive disorder.
  • The inherited deficiencies of galactokinase and UDP-galactose-4-epimerase also lead to minor types of galactosemia.
  • They all interfere with the normal metabolism of
  • galactose, causing a rise in blood and urine galactose.
  • Accumulation of galactose and galactose-1-phosphate in blood, liver, brain, kidney and eye lenses.
  • In these organs, galactose is reduced to galactitol (dulcitol) by the enzyme aldose reductase.

Biochemical Defect

  • Galactosemia is an inborn error of galactose metabolism due to the deficiency of enzyme Galactose-1-Phosphate Uridyl Transferase (GaliPUT).
  • This enzyme is responsible for conversion of galactose-1-phosphate to glucose-1-phosphate.

Abnormal Urine Constituent & Test

  • Since galactose remains unmetabolized, its level increases in blood in case of Galactosuria which gets filtered out in urine as an abnormal constituent.
  • Benedicts Test is done which gets positive result since galactose is a reducing agent.

Clinical Findings-

  • Liver failure and Hepatomegaly-
    • Lack of  Galactose-1-phosphate uridyl Transferase

enzyme impairs galactose metabolism and results in accumulation of galactose-1-phosphate in liver which results in hepatomegaly.

  • Mental retardation-
    • Accumulation of galacticol and galactose-1-phosphate in brain
  • Cataract formation-
    • Cataract formation is due to reduction of unmetabolized galactose in the lens of the eye in polyol pathway, where aldol reductase converts galactose to galactitol.
    • Galacticol being hygroscopic absorbs water into the lens cells which initiates cataract formation.
    • Cataract is bilateral, mostly mild, transient, and reversible.
  • Recurrent hypoglycemic attack:
    •  Accumulated galactose-1-phosphate inhibits glycogen phosphorylase enzyme which is manifested as recurrent hypoglycemic episodes.
    • Glycogen phosphorylase is the key enzyme in the liver to supply glucose in blood by glycogenolysis at the time of need.
    • Once inhibited, this enzyme does not run the glycogenolysis and results in recurrent hypoglycemia.
  • Icterus-
    • Galactose 1-phosphate accumulates in the liver.
    • Bilirubin uptake is less, and bilirubin conjugation is reduced.
    • So unconjugated bilirubin level is increased in blood leading to jaundice.

Treatment

  • Galactose in milk and milk products should be eliminated from the diet.
  • Sufficient galactose for the body’s need can be synthesized endogenously as UDP-galactose
  • Dietary treatment with lactose- and galactose-free diet if started early within 20 days of life can reverse cataract formation in galactosemic NBBs.
  • Baby can instead be given Soya milk