Disorders of Galactose Metabolism

Introduction

• Overview of galactose metabolism disorders.
• Focus on understanding the normal pathway and the diseases caused by enzymatic deficiencies.
• Use of mnemonics to aid memory for exams like USMLE or COMLEX.

Normal Galactose Metabolism Pathway

• Lactose Conversion:
  • Lactose is converted into glucose and galactose.
  • Enzyme involved: Lactase (breaks down lactose).
  • Occurs at the brush border of the small intestine.
• Galactose Conversion:
  • Galactose can be converted into:
    • Galactose 1-phosphate
    • Galactitol
  • Enzymes involved:
    • Aldose Reductase: Converts galactose into galactitol.
    • Galactokinase: Converts galactose into galactose 1-phosphate.
    • Important note: 'Kinase' indicates adding a phosphate group.
• Galactose 1-phosphate:
  • Converted into glucose 1-phosphate via Galactose-1-phosphate uridyltransferase.
  • Requires UDP glucose conversion to UDP galactose as a cofactor.

Diseases and Enzymatic Deficiencies

1. Galactokinase Deficiency

• Pathophysiology:
  • Inability to convert galactose into galactose 1-phosphate.
  • Accumulation of galactitol.
• Clinical Findings:
  • Galactosemia (galactose in blood)
  • Galactosuria (galactose in urine)
  • Abnormal eye tracking
  • Lack of social smile
  • Infantile cataracts (not severe)
• Mnemonic: "GALAC"
  • G: Galactosemia
  • A: Abnormal eye tracking
  • L: Lack of social smile
  • A: Autosomal recessive
  • C: Cataracts
• Severity: Generally not severe.

2. Classic Galactosemia (Severe)

• Enzyme Deficiency:
  • Galactose-1-phosphate uridyltransferase deficiency.
• Pathophysiology:
  • Severe accumulation of galactitol and galactose.
• Symptoms:
  • Severe cataracts
  • Hepatomegaly (liver enlargement)
  • Autosomal recessive
  • E. coli sepsis
  • Symptoms onset with feeding (e.g., vomiting after milk)
  • Intellectual disability
  • Jaundice (skin color change)
• Mnemonic: "CLASSIC"
  • C: Cataracts
  • L: Liver enlargement
  • A: Autosomal recessive
  • S: Sepsis
  • S: Start of feeding
  • I: Intellectual disability
  • C: Color changes
• Treatment: Avoid galactose/lactose in diet.

3. Lactose Intolerance

• Types:
  • Primary: Age-related decline in lactase activity, common in African-Americans, Asians, Native Americans.
  • Secondary: Post-viral (e.g., after gastroenteritis), damage to the intestinal brush border.
• Symptoms:
  • Bloating, gas, diarrhea
  • Increased h2, CH4, organic acids in breath
  • Decreased stool pH
• Histological Finding:
  • Normal intestinal mucosa (important differential feature)

Conclusion

• Understanding the pathway, enzymes, and symptoms of galactose metabolism disorders is crucial for exam success.
• Focus on high-yield points like enzyme deficiencies and associated clinical findings.