A 5-year-old child had a history of chronic diarrhea starting from the first month of life. His parents were related, and three other siblings were in good health. During the pregnancy, dilated bowel loops without polyhydramnios were demonstrated by ultrasound. After 37 weeks' gestation the baby was delivered by caesarean section with an Apgar score of 8/9 and a birth weight of 3200 g. At two weeks of age, meconium absence led to suspicion of Hirschsprung's disease. Thus, anal manometry and histochemical stains of rectal biopsy for acetylcholinesterase were performed showing normal results. Subsequently, in the following months and years, he developed chronic diarrhea (10–12 evacuations of liquid stool daily), without abdominal pain or rectal bleeding. Most bowel movements were associated with urgency or incontinence, and the child could not attend school because of diarrhea. By the age of 5 years, the family had moved to our city and the patient was re-evaluated. More recently, he had been admitted two times to an emergency department for severe dehydration due to gastroenteritis. Except for moderate abdominal distension and mild dehydration, the physical examination was normal. Laboratory tests showed normal erythrocyte sedimentation rate, and electrolytes, immunoglobulin, urea, creatinine, alkaline phosphatase, and albumin levels. Fecal quantitative fat measurement was not performed because of stool liquid consistency. Reducing substances were absent in feces and lactose hydrogen breath test, fecal alfa-1-antitrypsin, xylose absorption, and stool microbiologic tests were normal. Fecal osmotic gap was 64. Jejunal biopsy by endoscopy was performed. Endoscopic and histologic pictures were normal. X-ray evaluation of the intestine was also normal. Electron microscopy of jejunal biopsy specimen is shown in Figure 1.FIG. 1.: Electron microscopy of jejunal biopsy specimen.what is the etiology of diarrhea? A. Glucose and galactose malabsorption B. Congenital chloride diarrhea D. Primary bile acid malabsorption E. Intestinal epithelial dysplasia F. Small bowel overgrowth The electron microscopy of jejunal biopsy specimen was normal, thus excluding intestinal epithelial dysplasia. The patient was affected by congenital chloride diarrhea (B). In fact, fecal Cl−, Na+, and K+ concentrations were 180, 48, and 60 mmol/l respectively. Comment: The two diagnostic criteria of congenital chloride diarrhea (CCD) were fulfilled by the measurement of fecal electrolytes: Cl− content >90 mmol/L and > Na+ + K+ content (1). CCD is an inherited congenital defect of intestinal ion transport due to a mutation in the solute carrier family 26, member 3 (SLC26A3) gene at chromosomal location 7q31, close to the cystic fibrosis transmembrane conductance regulator (CFTR) gene (1,2). In CCD, the Cl−/HCO3− exchanger is absent or defective, causing severe intestinal Cl− malabsorption. Massive losses of Cl− in stools and the related defect in HCO3− secretion induce an acidification of intestinal lumen, which in turn further inhibits Na+ absorption through Na+/H+ exchanger activity. Thus, in the intestinal lumen high electrolyte content leads to osmotic diarrhea (2). Frequently the affected patients do not pass meconium and Hirschsprung's disease could be suspected. Our case is a sporadic form. Sporadic patients from different populations usually have two previously unrecognized unique mutations in their SLC26A3 alleles with no previous suspicion of CCD in the family, that suggests that mutations in the SLC26A3 gene are relatively frequent, and that the actual number of patients may be underestimated. The clinical picture and outcome of the disease could vary significantly from severe neonatal disease with fulminant hypoelectrolytemia and dehydration, to a relatively mild chronic form which remains undiagnosed for long time. Finally, early diagnosis is essential because hyponatremic episodes in infancy may result in mental and psychomotor impairment, and the chronic contraction of the intravascular space could induce renal impairment and gout. Many therapeutic strategies to reduce diarrhea, including cholestyramine and omeprazole, have proven to be ineffective (1,3). Therapy consists of oral supplements of sodium and potassium chloride. Ideally, the intestinal ion concentrations should be only slightly higher than in plasma, enabling net absorption of both electrolytes and water.
Read full abstract
Jan 1, 2012
Seon Min Yim + 4
Open Access
