title: Long-term clinical outcome in patients with congenital chloride diarrhea.
abstract: OBJECTIVE
  Congenital chloride diarrhea (CLD) is a rare, autosomal recessive disorder of intestinal Cl/HCO3 exchange caused by mutations in the SLC26A3 gene and characterized by persistent Cl rich diarrhea from birth. Treatment is symptomatic and replacement therapy with NaCl and KCl has been shown to be effective in children, but the long-term prognosis remains unclear. We studied the largest known cohort of patients to evaluate the long-term outcome of CLD and to search for extraintestinal manifestations.
  
  
  METHODS
  This is a cross-sectional clinical evaluation and retrospective analysis of medical history of 36 Finnish patients with CLD, born in the 1960s (n = 8), 1970s (n = 7) and 1980s (n = 21).
  
  
  RESULTS
  Early diagnosis and aggressive salt replacement therapy were associated with normal growth and development, in addition to significantly reduced mortality rates among the groups of patients born in the different decades, respectively (P = 0.001). No deaths due to CLD were observed after 1972. Enuresis, slight soiling and hospitalizations for gastroenteritis were common, especially in childhood, but 92% of the patients found their health excellent or good. Complications documented were end-stage renal disease (n = 1) and hyperuricemia (n = 4), novel findings possibly associated with CLD being male subfertility (n = 3), spermatoceles (n = 3), intestinal inflammation (n = 2), inguinal hernias (n = 4) and increased concentrations of sweat Cl in 12% of the patients.
  
  
  CONCLUSIONS
  When early diagnosed and adequately treated, the long-term prognosis of CLD is favorable. A putative role of a primary anion exchange defect of SLC26A3 in male subfertility and the decline of renal function due to chronic dehydration deserve further characterization.
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. satu.hihnala@helsinki.fi
authors.forename: Satu
authors.initials: S
authors.lastname: Hihnala
authors.forename: Pia
authors.initials: P
authors.lastname: Höglund
authors.forename: Laura
authors.initials: L
authors.lastname: Lammi
authors.forename: Jorma
authors.initials: J
authors.lastname: Kokkonen
authors.forename: Timo
authors.initials: T
authors.lastname: Ormälä
authors.forename: Christer
authors.initials: C
authors.lastname: Holmberg
mesh_terms: D000293:Adolescent; D000328:Adult; D017920:Antiporters; D002648:Child; D002675:Child, Preschool; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism* / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D003967:Diarrhea / Q000151:congenital / Q000235:genetics* / Q000628:therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011379:Prognosis; D011788:Quality of Life; D012189:Retrospective Studies; D000076988:Sulfate Transporters; D016896:Treatment Outcome
chemical_list: D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; C081011:SLC26A3 protein, human; D000076988:Sulfate Transporters