Lactose Intolerance and Galactosemia

Lactose Intolerance - Milk Mayhem

• Lactase (β-galactosidase) deficiency → maldigestion of lactose (glucose + galactose).
• Types:
  • Primary: Adult-type hypolactasia. Genetically programmed ↓ lactase. Most common. Autosomal Recessive (AR).
  • Secondary: Gut mucosal injury (e.g., gastroenteritis, celiac disease, IBD).
  • Congenital: Rare, AR. Neonatal onset.
  • Developmental: Preterm infants (< 34 wks gestation).
• Pathophysiology: Undigested lactose → osmotic diarrhea. Colonic bacterial fermentation → gas ($H_2$, $CO_2$, $CH_4$), short-chain fatty acids → bloating, flatulence, cramps.
• Clinical Features: Dose-dependent abdominal pain, bloating, diarrhea, flatulence post-lactose ingestion.
• Diagnosis:
  • Lactose Hydrogen Breath Test: ↑ $H_2$ in breath post-lactose (gold standard).
  • Lactose Tolerance Test: Blood glucose ↑ < 20 mg/dL over baseline after 50g oral lactose.
  • Stool pH < 5.5; reducing substances (+).
• Management: Dietary lactose restriction/avoidance. Lactase enzyme supplements. Calcium supplementation (if dairy avoided).
• 

⭐ Primary lactase deficiency (adult-type hypolactasia) is the most common form, typically developing after weaning due to genetic downregulation of lactase activity_._

Galactosemia - Sweet Poison

• Autosomal recessive disorders of galactose metabolism. Galactose from lactose (milk sugar) breakdown.
• Types & Deficiencies:
  • Classic (Type I): Galactose-1-Phosphate Uridyltransferase (GALT) deficiency. Most common & severe.
    • Accumulation: Galactose-1-phosphate (toxic), Galactitol.
  • Type II: Galactokinase (GALK) deficiency.
    • Accumulation: Galactose, Galactitol (cataracts).
  • Type III: UDP-Galactose-4-Epimerase (GALE) deficiency. Variable severity.
• Clinical Features (Classic GALT): Onset with milk feeding.
  • Jaundice, hepatomegaly, vomiting, FTT.
  • Cataracts (galactitol accumulation).
  • Neurological: Lethargy, hypotonia, developmental delay.
  • ⭐ > Neonates with GALT deficiency are at high risk for E. coli sepsis.
• Diagnosis:
  • Newborn screening (GALT activity).
  • ↑ Blood galactose, ↑ RBC galactose-1-phosphate.
  • Reducing substances in urine (non-glucose).
  • Enzyme assays, genetic testing.
• Management: Lifelong galactose-free diet (avoid milk, dairy). Soy-based formula.
• Prognosis: Early diagnosis & treatment crucial. Long-term complications (speech, ovarian failure) can occur despite diet.

Differential Diagnosis - Milk vs. Galactose

Lactose Intolerance

• Enzyme Defect: ↓ Lactase (β-galactosidase) at intestinal brush border.
• Onset: Variable: childhood to adulthood (primary); any age (secondary to gut damage).
• Pathophysiology: Undigested lactose ferments in colon → gas (H₂, CO₂, CH₄), acidic osmotic diarrhea.
• Clinical Features: GI symptoms post-lactose: bloating, abdominal cramps, flatulence, watery/frothy diarrhea. No systemic toxicity.
• Urine Reducing Substances: Negative.
• Diagnostic Clue: Positive hydrogen breath test (↑ H₂).
• Management: Dietary lactose restriction; lactase enzyme supplements.

Galactosemia (Classic - GALT Deficiency)

• Enzyme Defect: ↓ Galactose-1-Phosphate Uridyltransferase (GALT). Autosomal recessive.
• Onset: Neonatal period (days after initiating milk feeds).
• Pathophysiology: Accumulation of Galactose-1-Phosphate (cellular toxin) & Galactitol (osmotic damage, e.g., cataracts).
• Clinical Features: Severe, systemic: Failure to thrive (FTT), jaundice, hepatomegaly, vomiting, diarrhea, infantile cataracts, lethargy, hypotonia, intellectual disability.

  ⭐ High risk of neonatal E. coli sepsis in GALT deficiency.

• Urine Reducing Substances: Positive (due to galactose); test before glucose oxidase.
• Diagnostic Clue: ↓ GALT activity in RBCs; detected on newborn screening.
• Management: Strict, lifelong galactose-free diet (eliminate all milk, dairy, and galactose sources).

High‑Yield Points - ⚡ Biggest Takeaways

• Lactose intolerance: Caused by lactase deficiency, leading to diarrhea and bloating post-lactose; diagnosed by hydrogen breath test.
• Classic galactosemia: Due to GALT deficiency, causing galactose-1-phosphate accumulation; presents with failure to thrive, jaundice, hepatomegaly, cataracts, E. coli sepsis.
• Galactokinase deficiency: Results in infantile cataracts from galactitol accumulation.
• Galactosemias show non-glucose reducing substances in urine.
• Management for both involves dietary restriction: lactose-free or galactose-free_._