Clinical Case: Lactose Intolerance (Lactase Deficiency) in a 1-Year-Old

Q1 - Likely Cause

• Diarrhea, abdominal pain, and flatulence in a 1-year-old
• Symptoms worst in the late morning (after morning milk feeds)
• Worsens with milk intake - the key trigger
• No blood in stool - rules out inflammatory/invasive causes
• Perianal excoriation - caused by acidic stools from bacterial fermentation of undigested lactose in the colon

1. It acts as an osmotic load drawing water into the lumen (osmotic diarrhea)
2. Colonic bacteria ferment it, producing H₂, CO₂, and methane (flatulence, bloating)
3. Short-chain fatty acids produced make the stool acidic, causing perianal excoriation

Q2 - How to Diagnose

• The patient ingests a standard lactose load (1-2 g/kg in children)
• Undigested lactose is fermented by colonic bacteria producing hydrogen
• A rise in expired breath hydrogen of >20 ppm above baseline within 2-3 hours = positive test
• Simultaneously, symptoms (diarrhea, bloating, cramps) during the test confirm clinical relevance

• Lactose tolerance test: Oral lactose load followed by serial serum glucose measurements - a rise of <20 mg/dL indicates malabsorption (less preferred due to false positives)
• Stool pH: pH <5.5 is suggestive; stool reducing substances >0.5 g/dL considered abnormal (Clinitest on stool)
• Lactose-free dietary trial: Rapid, practical first approach - resolution of symptoms on a lactose-free diet is strong presumptive evidence

Q3 - Two Conditions Where Lactase Deficiency Occurs TRANSIENTLY

1. Acute viral gastroenteritis (e.g., rotavirus infection) - the most common cause of transient lactase deficiency in infants; villous blunting recovers after infection
2. Celiac disease (gluten-sensitive enteropathy) - mucosal damage from gluten causes secondary loss of lactase; improves with a gluten-free diet

Q4 - Confirmatory Biopsy

• A mucosal biopsy of the small intestine (typically from the duodenum/jejunum via upper GI endoscopy) is taken
• The biopsy specimen is subjected to biochemical assay measuring specific lactase enzyme activity in the mucosa (Dahlqvist assay)
• Demonstration of low specific lactase activity in the mucosal specimen is the definitive/gold-standard confirmatory test
• This is particularly useful to distinguish primary from secondary lactase deficiency, as secondary causes show abnormal mucosal architecture plus reduced enzyme activity

Note: The biopsy will show normal villous architecture in primary/genetic lactase deficiency (the enzyme is absent, but the mucosa looks normal), whereas secondary causes show villous atrophy.

Q5 - Dietary Advice

1. Eliminate or restrict lactose-containing foods: Avoid cow's milk, formula with lactose, cheese, ice cream, butter, and other dairy products
2. Lactose-free alternatives:
   • Use lactose-free milk/formula (hydrolyzed lactose or soy-based formula)
   • Rice milk, oat milk as alternatives
3. Maintain calcium intake: Dairy is the main calcium source; supplement with calcium-fortified foods or calcium supplements to prevent deficiency in a growing infant
4. Gradual reintroduction: Some children tolerate small amounts of lactose, especially in fermented forms (yogurt, hard cheese have lower lactose due to bacterial fermentation) - test tolerance individually
5. Read food labels: Lactose is a "hidden" ingredient in many processed foods, breads, and medications
6. For secondary lactase deficiency: The dietary restriction is temporary - lactose can be reintroduced gradually once the underlying illness (e.g., gastroenteritis, celiac disease) is treated
7. Lactase enzyme supplements: Commercially available lactase drops can be added to milk before feeding to help digest lactose

Q1 - Likely Cause (1M)

• Undigested lactose draws water osmotically → osmotic diarrhea
• Colonic bacteria ferment lactose → H₂, CO₂, methane → flatulence and bloating
• Acidic short-chain fatty acids produced → acidic stools → perianal excoriation
• Symptoms peak in late morning because that is when the morning milk feed has reached the colon

Q2 - How to Diagnose (1M)

Q3 - Two Conditions Where Lactase Deficiency Occurs TRANSIENTLY (1M)

1. Acute viral gastroenteritis (especially rotavirus) - most common cause in infants; villous blunting causes temporary loss of lactase
2. Celiac disease (gluten-sensitive enteropathy) - mucosal damage from gluten causes secondary lactase loss; resolves on a gluten-free diet

Other recognized causes: Giardia infection, tropical sprue, bacterial enteritis, drugs (neomycin, methotrexate)

Q4 - Confirmatory Biopsy (1M)

• Biopsy obtained from duodenum/jejunum via upper GI endoscopy
• Specimen sent for biochemical measurement of lactase enzyme activity (Dahlqvist assay)
• Finding of low specific lactase activity in mucosal tissue = gold standard/definitive confirmation
• In primary lactase deficiency: villous architecture is normal (structural mucosa intact, only enzyme absent)
• In secondary lactase deficiency: villous atrophy + reduced enzyme activity both present

Q5 - Dietary Advice

Cow's Milk Protein Allergy (CMPA) vs. Lactose Intolerance

Why This Case is NOT CMPA

1. No blood in stool - blood/mucus in stool is the hallmark of CMPA (especially the non-IgE colitis type seen in infants). The mother explicitly has not noticed blood.
2. Flatulence is a prominent feature - this is the direct result of bacterial fermentation of undigested lactose producing gas. In CMPA, flatulence is not a dominant symptom.
3. Perianal excoriation from acidic stools - this is characteristic of carbohydrate malabsorption (lactose intolerance), where fermentation produces short-chain fatty acids making stool pH <5.5. CMPA produces mucusy/bloody stools, not markedly acidic ones.
4. No systemic allergic features - no eczema, urticaria, wheeze, or vomiting mentioned, which would be expected in CMPA.

Bottom Line for Exams

Both worsen with milk. The key discriminators are:

• Blood/mucus in stool + no flatulence + skin/respiratory features → think CMPA
• No blood + prominent flatulence + acidic perianal excoriation → think Lactose Intolerance

Types of Primary Lactase Deficiency - and Why Age Matters

Why This Case is NOT Congenital (Primary) Lactase Deficiency

"Congenital lactase deficiency is quite rare and would have presented much earlier - from the first feeds on breast milk or formula at birth, with severe diarrhea and failure to thrive from day 1."

• Lippincott Biochemistry, 8th ed.

"Congenital deficiency of lactase occurs rarely in infants, leading to lactose intolerance and failure to thrive when fed on breast milk or normal infant formula."

• Harper's Illustrated Biochemistry, 32nd ed.

Why This Case is NOT Primary Adult-Type Hypolactasia Either

• Develops after weaning, with lactase levels declining progressively
• Typically becomes symptomatic between ages 5-10 years (when enzyme levels drop to ~10% of neonatal values)
• Rarely causes significant symptoms at 1 year of age

So What IS This Case?

Secondary lactase deficiency (most likely post-infectious / post-gastroenteritis) is the best answer, because:

• Congenital = presents at birth with failure to thrive ❌
• Adult-type primary = too early at 1 year ❌
• Secondary = fits the age, clinical context, and the fact that Q3 asks about transient causes ✅

Quick Memory Hook

Complications of Liver Abscess

A. Complications of PYOGENIC Liver Abscess

1. Rupture and Spread

2. Vascular Complications

3. Cardiac

• Pericardial effusion / rupture into pericardium → cardiac tamponade

4. Metastatic / Distant Complications (especially Klebsiella pneumoniae liver abscess)

⚠️ In K. pneumoniae liver abscess, the main concern today is not just mortality but catastrophic disability from irreversible ocular or CNS complications - a recognised syndrome of metastatic septic complications.

B. Complications of AMOEBIC Liver Abscess

Rupture - Three Main Directions:

• Transdiaphragmatic rupture → empyema (pleural space fills, lung collapses, "white-out" on CXR)
• Bronchohepatic fistula - abscess ruptures into bronchi → sudden cough with copious brown ("anchovy sauce") sputum - pathognomonic
• Pleuropulmonary abscess

• Ranges from asymptomatic pericardial effusion → acute pericarditis → cardiac tamponade → intrapericardial rupture (life-threatening)
• Left lobe abscesses are proximate to pericardium - always monitor with imaging

• Peritonitis - occurs in 78% via direct liver rupture; 22% via necrotizing amebic colitis
• Free rupture uncommon; usually the abscess is walled off by omentum/diaphragm

Other Sites (haematogenous spread)

Summary Table - Key Complications at a Glance

Exam Memory Hook

"PEPPER-B" for Pyogenic complications: Peritonitis, Empyema, Pericardial effusion, Portal vein thrombosis, Endophthalmitis (Klebsiella), Renal failure, Bacteraemia/sepsis

"BPPC" for Amoebic rupture directions: Bronchohepatic fistula (brown sputum), Peritonitis, Pericardial tamponade (left lobe), CNS/cerebral

Clinical Case Analysis: 14-year-old Female with Abdominal Pain + Ascending Flaccid Paralysis

Cracking the Case - Key Clues

Q1 - Differential Diagnosis (2 marks)

1. Acute Intermittent Porphyria (AIP) ← Most likely

• Autosomal dominant deficiency of porphobilinogen (PBG) deaminase
• Classic triad: abdominal pain + neuropsychiatric features + autonomic dysfunction
• Mimics GBS but additionally has hypertension, tachycardia, hyponatraemia, and dark urine

2. Guillain-Barré Syndrome (GBS)

• Post-infectious ascending flaccid paralysis with areflexia
• BUT: GBS does NOT cause abdominal pain as a primary feature, does NOT cause hypertension/tachycardia of this degree, does NOT cause hyponatraemia, and does NOT cause dark urine
• GBS usually follows respiratory/GI infection by 2-4 weeks

• Hypokalemic periodic paralysis - but K is normal (4) here, rules it out
• Botulism - descending (not ascending) paralysis
• Tick paralysis - ascending flaccid paralysis, but no abdominal features
• Transverse myelitis - but would give upper motor neuron signs

Q2 - Probable Diagnosis (1 mark)

Na 110 (severe hyponatraemia) + high-coloured urine + abdominal pain + ascending paralysis + hypertension/tachycardia

✅ ACUTE INTERMITTENT PORPHYRIA (AIP)

Q3 - Confirmatory Investigation (1 mark)

Urine Porphobilinogen (PBG) estimation - in a 24-hour urine collection or spot urine

• During acute attacks: urinary ALA (delta-aminolaevulinic acid) and PBG are markedly elevated
• PBG excretion exceeds ALA in AIP specifically
• A rapid bedside screening test: Watson-Schwartz test (urine turns pink/red with Ehrlich's aldehyde reagent)
• Urine turns dark red/port-wine on standing in light - visual confirmation

"The indispensable test that allows the diagnosis of an acute attack of autosomal dominant porphyria is urine porphobilinogen (PBG)."

• Tietz Textbook of Laboratory Medicine, 7th ed.

"Diagnosis is established by identification of large amounts of ALA and PBG in 24-hour urine during acute attacks, with PBG excretion exceeding ALA."

• Yamada's Textbook of Gastroenterology, 7th ed.

Q4 - Treatment (1 mark)

Acute Attack:

Prevention of Future Attacks:

• Givosiran (Givlaari) - monthly SC injection; siRNA that silences hepatic ALAS1 mRNA; FDA/EMA approved 2019; markedly reduces attack frequency
• GnRH analogues - for attacks triggered by luteal phase of menstrual cycle
• Liver transplantation - last resort for intractable, life-threatening attacks

Summary Card

Key distinguisher from GBS: GBS does NOT cause hypertension, tachycardia, hyponatraemia, or dark urine. AIP does all four.

Q1 - Differential Diagnosis (2 marks)

1. Acute Intermittent Porphyria (AIP) ← Primary differential

• Autosomal dominant; deficiency of PBG deaminase
• Strong female predominance; often triggered at puberty by hormonal changes
• Classic features: severe colicky abdominal pain + motor neuropathy (ascending weakness, areflexia) + autonomic dysfunction (hypertension, tachycardia)

2. Guillain-Barré Syndrome (GBS)

• Post-infectious ascending flaccid paralysis with areflexia
• Can cause autonomic instability
• BUT: does not typically cause primary abdominal pain, does not cause hyponatraemia, and does not cause dark urine

• Hypokalemic periodic paralysis (ruled out - K is normal)
• Transverse myelitis (would give UMN signs, not LMN/flaccid)
• Botulism (descending, not ascending)

Q2 - Probable Diagnosis (1 mark)

✅ Acute Intermittent Porphyria (AIP)

The combination of abdominal pain + ascending motor neuropathy + autonomic instability + hyponatraemia + dark urine = AIP until proven otherwise.

Q3 - Confirmatory Investigation (1 mark)

Urine Porphobilinogen (PBG) - spot urine or 24-hour urine collection

• During acute attack: urinary ALA (delta-aminolaevulinic acid) and PBG are markedly elevated
• PBG excretion exceeds ALA in AIP specifically
• Watson-Schwartz test (bedside): urine turns pink-red with Ehrlich's aldehyde reagent - rapid screening
• Urine left in sunlight turns dark red spontaneously

"The indispensable test that allows the diagnosis of an acute attack of autosomal dominant porphyria is urine porphobilinogen (PBG)."

• Tietz Textbook of Laboratory Medicine, 7th ed.

Q4 - Treatment (1 mark)

Acute Attack - Two pillars:

Long-term prevention:

• Givosiran (Givlaari) - monthly SC siRNA injection; silences ALAS1 mRNA; FDA-approved 2019; reduces attack frequency dramatically
• GnRH analogues - for attacks linked to luteal phase of menstrual cycle (relevant in this pubertal girl)

One-Line Summary Table

Exam tip - AIP vs GBS distinguishing features: