Distinct outcomes of chloride diarrhoea in two siblings with identical genetic background of the disease: implications for early diagnosis and treatment

Background-Congenital chloride diarrhoea (CLD, OMIM 214700) is a serious in herited defect of intestinal electrolyte absorption transmitted in an autos omal recessive fashion. The major clinical manifestation is diarrhoea with high chloride content which can be balanced by substitution. The molecular pathology involves an epithelial Cl-/HCO3- exchanger protein, encoded by th e solute carrier family 26, member 3 gene (SLC26A3), previously known as CL D or DRA (downregulated in adenomas). To date, almost 30 different mutation s in the SLC26A3 gene have been identified throughout the world. No clear g enotype-phenotype correlation has been established. Patients/methods-Two siblings presenting with CLD were studied for disease history, supplementation, or other treatments, and for mutations in the SLC 26A3 gene. Results-Mutatiom analysis revealed a homozygous I544N mutation i n both patients. However, despite the uniform genetic background of CLD in this family, the clinical picture and outcome of the disease were remarkabl y different between siblings. The older sibling had a late diagnosis and ch ronic course of the disease whereas the younger one, who was diagnosed soon after birth and immediately received supplementation therapy, grows and de velops normally. Conclusion-Time of diagnosis, substitution therapy, compliance, and compens atory mechanisms are more important modulators of the clinical picture of C LD than the type of mutation in the SLC26A3 gene.