Disorders of Galactose Metabolism

Overview

• Purpose: Discuss disorders related to galactose metabolism.
• Structure:
  • Normal biochemistry of lactose to galactose and further metabolism.
  • Enzyme deficiencies and resulting diseases.
  • Mnemonics to aid memory.

Galactose Metabolism Pathway

Lactose Conversion

• Lactose is converted to glucose and galactose by the enzyme lactase.
  • Occurs at the brush border of the small intestine.

Galactose Conversion

• Galactose is converted to:
  • Galactitol by aldose reductase.
  • Galactose 1-Phosphate by galactokinase.
    • Kinases add a phosphate group to reactants.

Galactose 1-Phosphate Conversion

• Enzyme: Galactose 1-phosphate uridyltransferase converts galactose 1-phosphate to glucose 1-phosphate.
• Cofactor: UDP glucose converts to UDP galactose in this step.

Glucose 1-Phosphate Options

• Can enter glycolysis, glycogenesis, or other biochemical pathways.

Enzyme Deficiencies and Diseases

Galactokinase Deficiency

• Pathway Change: Cannot convert galactose to galactose 1-phosphate; shunted to convert galactose to galactitol.
• Symptoms:
  • Galactosemia (galactose in blood).
  • Galactosuria (galactose in urine).
  • Abnormal eye tracking, lack of social smile, infantile cataracts.
  • Autosomal recessive.
• Mnemonic: "GALAC"
  • G: Galactosemia, Galactosuria
  • A: Abnormal eye tracking
  • L: Lack of social smile
  • A: Autosomal recessive
  • C: Cataracts

Classic Galactosemia

• Enzyme Deficiency: Galactose 1-phosphate uridyltransferase.
• Symptoms:
  • Severe cataracts, hepatomegaly (liver enlargement), susceptibility to E. coli sepsis.
  • Symptoms start with feeding.
  • Intellectual disability, jaundice.
  • Autosomal recessive.
• Mnemonic: "CLASSIC"
  • C: Cataracts
  • L: Liver enlargement
  • A: Autosomal recessive
  • S: Sepsis
  • S: Start of feeding
  • I: Intellectual disability
  • C: Color changes (jaundice)
• Treatment: Avoid lactose and galactose in diet.

Lactose Intolerance

• Types:
  • Primary: Age-dependent decline in lactase activity.
  • Secondary: Post-viral (e.g., post-gastroenteritis) damage to intestinal brush border.
• Symptoms: Increased H2 in breath, bloating, diarrhea, decreased stool pH.
• Histology: Normal intestinal mucosa.
  • High-yield buzzword for differentiating from other GI pathologies.

Key Takeaways

• Know the biochemistry pathway, enzyme deficiencies, and resulting diseases.
• Focus on symptoms of galactokinase deficiency and classic galactosemia.
• Use mnemonics for memory aids.