Rare Pulmonology News

Disease Profile

Congenital chloride diarrhea

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

P78.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CLD; Diarrhea 1, secretory chloride, congenital; DIAR1;

Categories

Congenital and Genetic Diseases; Digestive Diseases

Summary

Congenital chloride diarrhea (CCD) is a lifelong condition that causes large, watery stools (diarrhea) that contain an excess of chloride.[1] Those with CCD have diarrhea even before birth.[2] Signs of CCD before birth may be detected with an ultrasound, and may include an increased amount of amniotic fluid (polyhydramnios) and enlarged (dilated) intestinal loops in the fetus.[3] Newborns with CCD are often premature and may have a swollen-looking abdomen (abdominal distention).[4] For this reason, CCD is sometimes first mistaken for an intestinal obstruction.[5] CCD causes electrolyte imbalances including low blood sodium levels (hyponatremia) and chloride levels (hypochloremia).[4] Electrolyte imbalances and severe dehydration can lead to volume depletion (too little fluid surrounding body cells), loss of acid from the blood (metabolic alkalosis), hyperaldosteronism, delayed growth and development, and kidney damage (nephropathy).[2][4] Untreated CCD can ultimately be fatal within the first weeks or months of life.[3]

CCD is caused by mutations in the SLC26A3 gene and inheritance is autosomal recessive.[1][2][4] The diagnosis is based on detecting excessive chloride in the feces, when the newborn is in fluid and electrolyte balance.[4]

Treatment aims to control symptoms by replacing lost electrolytes and water, and typically involves oral or intravenous sodium chloride and potassium chloride.[4][5] Infants who are diagnosed and treated very shortly after birth have the potential to grow and develop normally.[5] If not treated adequately, CCD ultimately causes chronic kidney disease.[5]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating

[ more ]

0003270
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Alkalosis
0001948
Autosomal recessive inheritance
0000007
Dehydration
0001944
Diarrhea
Watery stool
0002014
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Growth abnormality
Abnormal growth
Growth issue

[ more ]

0001507
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hyperactive renin-angiotensin system
0000841
Hyperaldosteronism
Elevated plasma aldosterone
Increased aldosterone
Increased aldosterone production

[ more ]

0000859
Hypochloremia
Low blood chloride levels
0003113
Hypokalemia
Low blood potassium levels
0002900
Hyponatremia
Low blood sodium levels
0002902
Metabolic alkalosis
0200114
Polyhydramnios
High levels of amniotic fluid
0001561
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622

Treatment

Congenital chloride diarrhea (CCD) is a lifelong disease, so treatment focuses on managing symptoms and preventing complications. Early diagnosis and treatment in the absence of major complications can lead to normal growth and development.[6] The main treatment is called salt substitution therapy (receiving sodium chloride and potassium chloride). Newborns are first given this therapy intravenously (by IV) and are later transitioned to oral therapy.[7] Diarrhea will persist through therapy even when there is adequate salt substitution, although the relative amount of stool generally decreases with age.[7][3]

Treatment for episodes of acute gastroenteritis ("stomach flu") in children with CCD is extremely important because they can experience rapid dehydration and loss of potassium (hypokalemia). These episodes should be treated with IV replacement of fluids and electrolytes. In adulthood, people with CCD are usually able to avoid dehydration by taking extra salt substitution.[3]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • The Centers for Disease Control and Prevention (CDC) provides information on chronic diarrhea. The CDC is recognized as the lead federal agency for developing and applying disease prevention and control, environmental health, and health promotion and education activities designed to improve the health of the people of the United States.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital chloride diarrhea. Click on the link to view a sample search on this topic.

        References

        1. SLC26A3. Genetics Home Reference. February 13, 2011; https://ghr.nlm.nih.gov/gene/SLC26A3. Accessed 2/21/2011.
        2. Berendt W. Aichbichler, Charles H. Zerr, Carol A. Santa Ana, Jack L. Porter, and John S. Fordtran. Proton-Pump Inhibition of Gastric Chloride Secretion in Congenital Chloridorrhea. The New England Journal of Medicine. January 9, 1997; 336:106-109. https://www.nejm.org/doi/full/10.1056/NEJM199701093360205. Accessed 2/21/2011.
        3. Wedenoja S, Höglund P, Holmberg C. Review article: the clinical management of congenital chloride diarrhoea. Aliment Pharmacol Ther. February 15, 2010; 31(4):477-485. https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2009.04197.x/pdf.
        4. Kellermayer R, Shulman R. Overview of the causes of chronic diarrhea in children in resource-rich countries. UpToDate. Waltham, MA: UpToDate; December 6, 2017; https://www.uptodate.com/contents/overview-of-the-causes-of-chronic-diarrhea-in-children-in-resource-rich-countries.
        5. Kawamura T, Nishiguchi T. Congenital Chloride Diarrhea (CCD): A Case Report of CCD Suspected by Prenatal Ultrasonography and Magnetic Resonance Imaging (MRI). Am J Case Rep. June 24, 2017; 18:707-713. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493062/.
        6. Hihnala S, Höglund P, Lammi L, Kokkonen J, Ormälä T, Holmberg C.. Long-term clinical outcome in patients with congenital chloride diarrhea. Journal of Pediatric Gastroenterology and Nutrition. April 2006; 42(4):369-375. https://www.ncbi.nlm.nih.gov/pubmed/16641574. Accessed 2/21/2011.
        7. Pieroni KP, Bass D. Proton pump inhibitor treatment for congenital chloride diarrhea. Dig Dis Sci. March, 2011; 56(3):673-676. https://www.ncbi.nlm.nih.gov/pubmed/21127979.
        8. Marla J. F. O'Neill. DIARRHEA 1, SECRETORY CHLORIDE, CONGENITAL; DIAR1. OMIM. January 12, 2010; https://www.ncbi.nlm.nih.gov/omim/214700. Accessed 2/21/2011.
        9. Canani RB, Terrin G, Cirillo P, Castaldo G, Salvatore F, Cardillo G, Coruzzo A, Troncone R. Butyrate as an effective treatment of congenital chloride diarrhea. Gastroenterology. August 2004; 127(2):630-634. https://www.ncbi.nlm.nih.gov/pubmed/15300594. Accessed 2/21/2011.

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