Clinical Scenario:
A 3-month-old infant is brought with a history of persistent watery diarrhea since the first week of life. The stools are large in volume and continue despite fasting. The infant has poor weight gain and recurrent episodes of dehydration. On examination, there is abdominal distension but no fever or blood in the stool.
Investigations show:
- Serum Na⁺: 132 mmol/L
- Serum K⁺: 2.8 mmol/L
- Serum Cl⁻: 88 mmol/L
- HCO₃⁻: 38 mmol/L
- Blood pH: 7.49
- Urine chloride: low
- Stool chloride: 125 mmol/L
What is the most likely diagnosis?
A. Congenital chloride diarrhea
B. Congenital sodium diarrhea
C. Cystic fibrosis
D. Glucose-galactose malabsorption
E. Microvillus inclusion disease
Correct answer & Explanation:
Correct answer: A. Congenital chloride diarrhea
Explanation
Congenital chloride diarrhea (CCD) is an autosomal-recessive intestinal secretory disorder caused most commonly by mutations in the SLC26A3 gene, which encodes the intestinal Cl⁻/HCO₃⁻ exchanger.
The classic features are:
- Watery diarrhea beginning in the neonatal period
- High stool chloride concentration, typically >90 mmol/L
- Persistent diarrhea even during fasting
- Abdominal distension
- Failure to thrive
- Hypochloremic, hypokalemic metabolic alkalosis
- Low urine chloride due to chloride depletion
The combination of neonatal-onset watery diarrhea + high stool chloride + hypochloremic metabolic alkalosis is highly characteristic of CCD.
Why the other options are less likely:
- Congenital sodium diarrhea is characterized by excessive fecal sodium loss and usually causes a hypochloremic metabolic acidosis, in contrast to the metabolic alkalosis typical of congenital chloride diarrhea.
- Cystic fibrosis: diarrhea is usually related to pancreatic insufficiency and causes malabsorption rather than a markedly elevated stool chloride.
- Glucose-galactose malabsorption: diarrhea improves when glucose and galactose are removed from the diet.
- Microvillus inclusion disease: causes severe congenital secretory diarrhea, but does not characteristically produce the very high stool chloride with hypochloremic metabolic alkalosis seen in CCD.
High-yield pearl
Congenital chloride diarrhea → high stool Cl⁻ + hypochloremic hypokalemic metabolic alkalosis.
This is a particularly useful distinction from congenital sodium diarrhea, which tends to produce high stool Na⁺ and may be associated with metabolic acidosis.
Reference
- Gils C, Eckhardt MC, Nielsen PE, Nybo M. Congenital chloride diarrhea: diagnosis by easy-accessible chloride measurement in feces. Case Rep Pediatr. 2016;2016:2519498. doi:10.1155/2016/2519498.
- Di Meglio L, Castaldo G, Mosca C, Paonessa A, Gelzo M, Esposito MV, et al. Congenital chloride diarrhea clinical features and management: a systematic review. Pediatr Res. 2021;90(1):23-29. doi:10.1038/s41390-020-01251-2.
