Congenital secretory chloride diarrhea is characterized by chronic secretory diarrhea with an excess of chloride. Onset occurs prenatally causing complications such as polyhydramnios, preterm delivery, and lack of meconium at birth. Postnatal complications include dehydration, hypocholermic and hypokalemic metabolic alkalosis, and failure to thrive. If untreated, it leads to impaired renal function, nephrocalcinosis, and end stage renal disease. However, treatment with NaCl and KCl leads to normal growth and development.
Congenital secretory chloride diarrhea is inherited in an autosomal recessive manner. Most mutations are nonsynonymous point mutations (55%) followed by small deletions (27%), insertions (5%), or a combination (5%). A minority of patients have gross deletions (5%) or insertions (2%). There are founder mutations in the Finnish (c.951_953del), Arab (c.559G>T), and Polish (c.2024_2026dup) populations. The c.951_953del founder mutation has been identified in the homozygous state in all Finnish patients but one. The c.559G>T founder mutation accounts for >90% of disease causing mutations in the Arab population, and the c.2024_2026dup founder mutation is identified in approximately 50% of affected Polish individuals.
This laboratory performs Sanger sequencing of the SLC26A3 gene.