Lactase Deficiency: Genetics, Types & Pathophysiology of Lactose Intolerance

Lactase (LCT gene, chromosome 2) hydrolyzes lactose → glucose + galactose in small intestinal brush border.

Types of Lactase Deficiency

• Primary (Adult-Type Hypolactasia): Physiologic downregulation after weaning. Autosomal recessive. Prevalence: 70% global (high in Asian, African, Native American, Mediterranean). Onset: childhood–adulthood.
• Secondary: Villous atrophy from celiac, Crohn's, gastroenteritis, SIBO, chemo/radiation. Reversible if mucosa heals.
• Congenital (Alactasia): Rare autosomal recessive; neonatal watery diarrhea on milk. Requires lactose-free formula.
• Developmental: Preterm infants (<34 wks) — low lactase; improves with maturation.

Symptom Mechanism

Undigested lactose → osmotic load → water secretion → colonic fermentation by bacteria → SCFA + gas (H₂, CH₄, CO₂) → bloating, cramps, diarrhea (30 min–2 hr post-ingestion).

Diagnosis

• Hydrogen breath test (gold standard non-invasive).
• Lactose tolerance test (blood glucose rise <20 mg/dL).
• Genetic testing (LCT -13910 C>T) for primary type.