What is the treatment for Congenital Chloride Diarrhea (CCD)?

Treatment of Congenital Chloride Diarrhea

Lifelong oral salt replacement therapy with sodium chloride (NaCl) and potassium chloride (KCl) is the definitive treatment for congenital chloride diarrhea, which must be initiated immediately upon diagnosis to prevent life-threatening dehydration and electrolyte depletion. 1, 2

Acute Management in Newborns and Infants

Immediate Stabilization

• Initiate aggressive intravenous fluid resuscitation with isotonic saline to correct severe dehydration and hypovolemic shock, which is the primary cause of mortality in untreated cases 2, 3
• Correct hypochloremia, hypokalemia, and hyponatremia urgently, as these electrolyte disturbances can be lethal within the first months of life if inadequately treated 2, 4
• Monitor serum electrolytes closely during initial stabilization, as hypokalemia may resolve more rapidly than expected once fluid replacement begins 4

Diagnostic Confirmation

• Measure fecal chloride concentration after correcting water and electrolyte deficits; a level exceeding 90 mmol/L confirms the diagnosis 2, 5
• Use a standard blood gas analyzer to measure chloride in watery feces as a rapid preliminary test when CCD is suspected 5
• Confirm diagnosis with DNA testing for mutations in the SLC26A3 gene encoding the intestinal Cl⁻/HCO₃⁻ exchanger 1, 3

Long-Term Maintenance Therapy

Salt Replacement Regimen

• Provide full oral replacement of fecal losses of chloride, sodium, potassium, and water on a daily basis to maintain normal electrolyte balance and prevent secondary complications 2, 3
• Administer NaCl and KCl supplements continuously throughout life, as this therapy abolishes secondary metabolic disorders and enables normal growth and development 2
• Adjust salt supplementation doses based on stool output, which varies with age, diet, and intercurrent illness 1

Expected Outcomes with Treatment

• Normal growth and development can be achieved when salt replacement is adequate and initiated early 2, 3
• Diarrhea persists despite treatment but typically improves during adulthood in 91.3% of cases 3
• Most children achieve normal toilet training and social adjustment despite ongoing diarrhea 2

Management of Acute Complications

During Gastroenteritis or Infections

• Increase salt supplementation immediately during episodes of gastroenteritis or other infections to compensate for increased fecal losses 1
• Consider temporary intravenous fluid and electrolyte replacement if oral intake is inadequate or vomiting prevents oral therapy 1, 4
• Monitor for severe dehydration and hypokalaemia, which require aggressive correction 1

Metabolic Alkalosis Management

• Correct metabolic alkalosis through adequate chloride replacement rather than attempting to acidify with medications 2
• The alkalosis results from impaired intestinal HCO₃⁻ excretion and resolves with proper chloride supplementation 2

Monitoring and Follow-Up

Regular Surveillance

• Implement close multidisciplinary follow-up to detect and manage heterogeneous complications early 3
• Monitor growth parameters (weight, height, head circumference) at every visit to ensure adequate nutritional status 3
• Check serum electrolytes, renal function, and acid-base status regularly to adjust salt replacement doses 1, 3

Screening for Complications

• Evaluate for chronic kidney disease, which occurs in 17.7% of patients and results from chronic volume depletion and elevated renin-aldosterone levels 2, 3
• Screen for failure to thrive (21.6% incidence), which indicates inadequate salt replacement 3
• Monitor for intestinal inflammation, which can complicate the disease course 1
• Assess male patients for subfertility, a recognized extraintestinal manifestation 1

Critical Pitfalls to Avoid

Misdiagnosis Risk

• Do not confuse CCD with pseudo-Bartter syndrome, as both present with hypokalemia, metabolic alkalosis, and hypochloremia; however, CCD has profuse watery diarrhea and high fecal chloride (>90 mmol/L) 4
• Recognize that the median diagnostic delay is 60 days, during which inadequate treatment can cause irreversible complications or death 3

Treatment Errors

• Never attempt to stop the diarrhea with antimotility agents, as the diarrhea is caused by a genetic defect in intestinal chloride transport and cannot be eliminated 2
• Avoid treating metabolic alkalosis with acidifying agents like Shohl's solution or thiazides, as these do not address the underlying chloride deficit and may worsen outcomes 4
• Do not underestimate salt requirements during intercurrent illness, as inadequate supplementation during infections is a common cause of acute decompensation 1

Prevention of Secondary Complications

• Prevent renal disease by maintaining adequate hydration and electrolyte balance from diagnosis onward, as pathological kidney changes develop from chronic volume depletion and hyperreninemia 2
• Ensure adequate salt replacement to prevent grossly elevated plasma renin and aldosterone concentrations, which contribute to renal damage 2

Prenatal and Neonatal Considerations

Prenatal Diagnosis

• Consider prenatal molecular testing in families with known CCD mutations or in pregnancies with polyhydramnios (present in 98.3% of cases) 3
• Recognize that polyhydramnios results from intrauterine diarrhea and often leads to preterm delivery (78.6% of cases) 3

Neonatal Presentation

• Expect failure to pass meconium in 60.7% of affected newborns 3
• Anticipate diarrhea onset at a mean age of 6.63 days, with abdominal distension and profuse watery yellow stools 3, 5
• Initiate treatment immediately upon clinical suspicion without waiting for genetic confirmation, as delay increases mortality risk 1, 2