Introduction
Diarrhea is a condition of having more than three loose or watery stools a day. It may last for a few days, depending on the cause, and result in fluid loss and dehydration. The occurrence of diarrhea in young infants (less than six months of age) is relatively common. In most cases, it is caused by infection or food intolerance. Severe persistent diarrhea that begins within a few days of birth and lasts for several weeks indicates congenital defects of the intestine.
A group of genetic disorders that cause severe diarrhea and associated complications in newborns is collectively known as congenital diarrheal disorders. Congenital sodium diarrhea (CSD) is an inborn intestinal sodium or proton exchange disorder that results in hyponatremia and metabolic acidosis, severe diarrhea, and excessive, alkaline stool with high sodium concentrations.
What Are Congenital Diarrheal Disorders (CDDs)?
Congenital diarrheal disorders are rare genetic disorders that usually occur during the first week of life. Affected infants may have frequent chronic diarrhea, malabsorption, feeding intolerance, and retarded growth. For most congenital diarrheal disorders, the disease-causing gene is identified. Some examples of congenital diarrheal disorders, along with the gene mutation involved, are given below.
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Congenital chloride diarrhea - SLC26A3 gene.
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Congenital sodium diarrhea - SPLINT2, GUCY2C, and SLC9A3 gene.
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Microvillus inclusion disease - MYO5B, STXBP2, and STX3.
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Congenital tufting enteropathy - EPCAM (epithelial cell adhesion molecule).
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Congenital malabsorptive diarrhea - NEUROG 3.
What Is Congenital Sodium Diarrhea?
Congenital sodium diarrhea is a rare type of secretory diarrhea caused by a malfunction in the sodium or proton exchanger, which results in reduced salt absorption and greater sodium excretion in the stools. While the prevalence is unknown, less than 50 cases of congenital sodium diarrhea have been reported. Due to the very rare incidence of this condition, the exact genetic cause and associated symptoms are not yet fully understood. Based on the available data, the gene mutation that causes defective sodium or proton exchange in the apical membrane of epithelial cells of the small intestine leads to this inborn defect.
What Are the Causes of Congenital Sodium Diarrhea?
The exact etiology of congenital sodium diarrhea is not yet identified. However, based on the available cases, it is identified that gene mutation in the SLC9A3 (sodium hydrogen exchanger 3), GUCY2C (guanylate cyclase C), and SPLINT2 (serine peptidase inhibitor 2) genes are responsible for this condition. These gene mutations will disrupt the functions of sodium or hydrogen exchangers in the intestinal cells resulting in abnormal sodium absorption, diarrhea, and enhanced fluid secretion. The inheritance pattern for SLC9A3 mutations is autosomal recessive, while GUCY2C mutations are autosomal dominant. But in a few cases, relevant gene mutations have yet to be identified.
What Are the Clinical Symptoms Associated With Congenital Sodium Diarrhea?
The clinical presentation of congenital sodium diarrhea is typically prenatal, with abdominal distension and excessive amniotic fluid accumulation around the baby (polyhydramnios). Soon after the birth, severe watery diarrhea will be seen in the baby independent of feeding (breast milk or formula milk) or nothing by the mouth. The diarrhea is described as 'non-stopping,' and it is easily confused with urine. There are increased bowel sounds during the examination, but no meconium (first or early infant stool) is reported. The infants become agitated and eventually become indifferent, and they suffer from mild to severe dehydration.
How Is Congenital Sodium Diarrhea Diagnosed?
The diagnosis of congenital sodium diarrhea is made based on the clinical presentation. Determining fecal sodium, chloride, and potassium levels may be part of the initial diagnosis. Urine and watery stools should be sampled separately. Laboratory findings include high stool sodium levels and metabolic acidosis, low blood sodium levels, alkaline fecal pH, and low urinary sodium excretion. Histological findings include a structurally intact epithelium and a brush border with a normal villus-to-crypt ratio.
Antenatal diagnosis can be established based on the presence of polyhydramnios in the third trimester. Following the identification of disease-causing variations in an index patient, early, focused prenatal genetic testing is possible. Genetic testing is used to confirm the diagnosis of congenital sodium diarrhea.
What Are the Treatment Options for Congenital Sodium Diarrhea?
To address dehydration, total parenteral nutrition is needed for at least a few months after delivery. Supplemental sodium should be given to cure severe dehydration and to sustain healthy body growth by avoiding sodium loss from the entire body. The FENa (fractional excretion of sodium) should be assessed to monitor adequate sodium supplementation. The usual range is allegedly between 0.5 to 1.5 percent.
What Is the Differential Diagnosis of Congenital Sodium Diarrhea?
The differential diagnosis of congenital sodium diarrhea includes the syndromic form of congenital sodium diarrhea that occurs due to SPINT2 mutations. It is often differentiated by uni- or bilateral choanal atresia at birth. Other possible diagnoses include congenital tufting enteropathy, microvillus inclusion disease, glucose-galactose malabsorption, congenital chloride diarrhea, excessive fecal chloride, and congenital chloride diarrhea with excessive fecal chloride (distinguished by histopathology).
Conclusion
Congenital sodium diarrhea (CSD) is a rare cause of severe diarrhea that can manifest very early in life, even in infancy. It is a sodium or proton exchange disease. Due to the rare incidence of this condition, the exact etiology and clinical symptoms still need to be identified. Mutation in the SPLINT2, GUCY2C, and SLC9A3 genes is considered the cause of this defect. However, the exact reason and further treatment strategies are yet to be identified.
