OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: SPINT2

CSD
Diarrhea 3
DIAR3
Congenital sodium secretory syndrome

Diarrhea
Corneal erosions
Polyhydramnios
Choanal atresia
Hypertelorism
Anal atresia

Congenital Sodium Diarrhea

Clinical Characteristics

General description (for patients):

Sodium diarrhea is a relatively new syndrome recognized by life-threatening neonatal diarrhea and recurrent erosions (scratches) on the cornea and is often associated with malformations. The eyes may appear widely spaced, and there may be incomplete perforation of the anal opening with vaginal abnormalities in some females.  Excess amniotic fluid (birth water) is sometimes a feature.  It must be diagnosed early and treated vigorously with intravenous fluids and even then many infants die in the first year of life. Beyond infancy, vigorous fluid replacement is required as well but patients may live at least into the second decade.

Medical description: 

Congenital sodium diarrhea has been recognized in mostly isolated families since 1985. Recently, a syndromal hereditary form has been identified consisting of neonatal onset and life-threatening watery diarrhea, recurrent corneal erosions, hypertelorism, choanal and anal atresia, and maternal polyhydramnios. Hyponatremia and profound metabolic acidosis occur quickly, necessitating prompt and vigorous parenteral fluid replacement. Even so, some infants die in the first year of life and beyond the neonatal period careful monitoring and parenteral supplementation is required. No structural abnormalities in intestinal epithelium have been found and the cause seems to lie in a defect in metabolic regulation of intestinal sodium absorption or secretion of sodium.

Genetics:

Molecular defects in the SPINT2 gene on chromosome 19 (19q13.1) is responsible for the syndromic form of this disease (non-syndromic forms are known as well).Five splicing and missense mutations in homozygous or compound heterozygous states in these patients have been identified. A homozygous c488A>G missense mutation has been found in an Amish child in Ontario. Consanguinity and the familial nature of some cases suggest autosomal recessive inheritance which is consistent with the configuration of DNA mutations.

Treatment: 

Parenteral feeding and fluid replacement seems to be the only effective treatment. Hyponatremia and metabolic acidosis must be monitored and treated appropriately. Non-steroidal anti-inflammatory drops to the corneas can prolong the relapse intervals between episodes of painful erosions.

Prognosis:

Many infants do not live beyond the first year of life in spite of optimum therapy, and most of those who do require continued fluid and nutritional supplementation.

Ancillary treatments and support:

Infections of all types must be treated promptly and careful monitoring of feeding equipment is important.

Specialists and specialty centers:

Nutritionist, pediatrician, gastroenterologist

References:

Heinz-Erian, P., Müller, T., Krabichler, B., Schranz, M., Becker, C., Rüschendorf, F., Nürnberg, P., Rossier, B., Vujic, M., Booth, I.W., Holmberg, C., Wijmenga, C., Grigelioniene, G., Kneepkens, C.M., Rosipal, S., Mistrik, M., Kappler, M., Michaud, L., Dóczy, L.C., Siu, V.M., Krantz, M., Zoller, H., Utermann, G., Janecke, A.R.:   Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea.  Am. J. Hum. Genet. 84(2): 188-96, 2009.  PubMed ID:  19185281

Muller, T., Wijmenga, C., Phillips, A. D., Janecke, A., Houwen, R. H. J., Fischer, H., Ellemunter, H., Fruhwirth, M., Offner, F., Hofer, S., Muller, W., Booth, I. W., Heinz-Erian, P.:  Congenital sodium diarrhea is an autosomal recessive disorder of sodium/proton exchange but unrelated to known candidate genes.  Gastroenterology119: 1506-1513, 2000. PubMed ID: 11113072

Resources:

National Digestive Diseases Information Clearinghouse

Associated Graphics