Congenital chloride diarrhea

Last updated
Congenital chloride diarrhea
Other namesDarrow Gamble syndrome
Autosomal recessive - en.svg
This condition is inherited via autosomal recessive manner
Symptoms High volume diarrhea

High chloride concentration in stool (>90mmol/L) Low chloride excretion in the urine

Hypochloremic alkalosis and hypokalemia

Contents

Congenital chloride diarrhea (CCD, also congenital chloridorrhea or Darrow Gamble syndrome) is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma (DRA), a gene that encodes a membrane protein of intestinal cells. The protein belongs to the solute carrier 26 family of membrane transport proteins. [1] More than 20 mutations in the gene are known to date. A rare disease, CCD occurs in all parts of the world but is more common in some populations with genetic founder effects, [2] most notably in Finland.

Symptoms and signs

Chronic diarrhoea starting from early neonatal period. Failure to thrive is usually accompanying diarrhea.

Pathophysiology

CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive. [3]

Diagnosis

CCD may be detectable on prenatal ultrasound. [4] [5] After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/L. [5] An important feature in this diarrhea that helps in the diagnosis, is that it is the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis. [6]

Treatment

Available treatments address the symptoms of CCD, not the underlying defect. Early diagnosis and aggressive salt replacement therapy result in normal growth and development, and generally good outcomes. Replacement of NaCl and KCl has been shown to be effective in children. [7]

History

Observations leading to the characterization of the SLC26 family were based on research on rare human diseases. Three rare recessive diseases in humans have been shown to be caused by genes of this family. Diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome are caused by the highly related genes SLC26A2 (first called DTDST), SLC26A3 (first called CLD or DRA), and SLC26A4 (first called PDS), respectively. [8] Two of these diseases, diastrophic dysplasia and congenital chloride diarrhea, are Finnish heritage diseases. [9]

References

  1. ↑ Dorwart MR, Shcheynikov N, Yang D, Muallem S (April 2008). "The solute carrier 26 family of proteins in epithelial ion transport". Physiology. 23 (2): 104–14. doi:10.1152/physiol.00037.2007. PMID   18400693.
  2. ↑ Kere J, Lohi H, Höglund P (January 1999). "Genetic Disorders of Membrane Transport III. Congenital chloride diarrhea". The American Journal of Physiology. 276 (1 Pt 1): G7 –G13. doi:10.1152/ajpgi.1999.276.1.G7. PMID   9886972.
  3. ↑ Mäkelä S, Kere J, Holmberg C, Höglund P (December 2002). "SLC26A3 mutations in congenital chloride diarrhea". Human Mutation. 20 (6): 425–38. doi: 10.1002/humu.10139 . PMID   12442266. S2CID   2450225.
  4. ↑ Rose NC, Kaplan P, Scott S, Kousoulis A, Librizzi R (1992). "Prenatal presentation of congenital chloride diarrhea: clinical report and review of the literature". American Journal of Perinatology. 9 (5–6): 398–400. doi:10.1055/s-2007-999274. PMID   1418143.
  5. 1 2 Abdullah AM, Shaheed MM, Katugampola SM, Patel PJ (March 1990). "Congenital chloride diarrhoea: case report and review of the literature". Annals of Tropical Paediatrics. 10 (1): 71–4. doi:10.1080/02724936.1990.11747412. PMID   1694648.
  6. ↑ Hirakawa, M.; Hidaka, N.; Kido, S.; Fukushima, K.; Kato, K. (2015). "Congenital Chloride Diarrhea: Accurate Prenatal Diagnosis Using Color Doppler Sonography to Show the Passage of Diarrhea". Journal of Ultrasound in Medicine. 34 (11): 2113–2115. doi:10.7863/ultra.15.01011. ISSN   0278-4297. PMID   26446821.
  7. ↑ Hihnala S, Höglund P, Lammi L, Kokkonen J, Ormälä T, Holmberg C (April 2006). "Long-term clinical outcome in patients with congenital chloride diarrhea". Journal of Pediatric Gastroenterology and Nutrition. 42 (4): 369–75. doi: 10.1097/01.mpg.0000214161.37574.9a . PMID   16641574. S2CID   12078505.
  8. ↑ Kere J (2006). "Overview of the SLC26 Family and Associated Diseases". Epithelial Anion Transport in Health and Disease: The Role of the SLC26 Transporters Family. Novartis Foundation Symposia. Vol. 273. pp. 2–11, discussion 11–8, 261–4. doi:10.1002/0470029579.ch2. ISBN   9780470016244. PMID   17120758.{{cite book}}: |journal= ignored (help)
  9. ↑ Uusimaa, Johanna; Kettunen, Johannes; Varilo, Teppo; Järvelä, Irma; Kallijärvi, Jukka; Kääriäinen, Helena; Laine, Minna; Lapatto, Risto; Myllynen, Päivi; Niinikoski, Harri; Rahikkala, Elisa; Suomalainen, Anu; Tikkanen, Ritva; Tyynismaa, Henna; Vieira, Päivi; Zarybnicky, Tomas; Sipilä, Petra; Kuure, Satu; Hinttala, Reetta (2022-10-01). "The Finnish genetic heritage in 2022 – from diagnosis to translational research". Disease Models & Mechanisms. 15 (10). The Company of Biologists. doi:10.1242/dmm.049490. ISSN   1754-8403. PMC   9637267 .
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