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Prevalence
The SLC9A3-related disorder—an autosomal-recessive form of congenital secretory sodium diarrhea (CSD)—is very rare (estimated prevalence <1/1,000,000).

Clinical characteristics
Females carrying a child with autosomal-recessive CSD typically present antenatally with polyhydramnios in the third trimester. Following birth, neonatal infants produce a profuse watery diarrhea with high fecal and low serum sodium levels, alkaline fecal pH and metabolic acidosis (due to decreased renal secretion of intracellular H⁺ accompanied by reduced reabsorption of luminal bicarbonate (HCO₃⁻)). Tissue histological analyses reveal normal morphology of the epithelium and brush border. Infants become irritable and eventually lethargic, and exhibit moderate to severe dehydration, failing to thrive if untreated. Afflicted individuals may require prolonged sodium and bicarbonate supplementation in early life; growth may normalize if carefully managed.

Other reported features observed in some patients with defective SLC9A3include the later development of ileal/colonic ulceration and inflammatory‐bowel‐disease (IBD)-like features during childhood and adolescence (variable expressivity) and potentially male infertility (if present in cystic fibrosis patients).

Inheritance
For the congenital sodium diarrhea phenotype, the inheritance is autosomal recessive: two loss‐of‐function or strongly hypomorphic SLC9A3 alleles (homozygous or compound heterozygous) have been documented.

For the reproductive/CBAVD modifier role in cystic fibrosis disease, the SLC9A3 variants may act in heterozygous state or as part of a multi‐gene context (i.e., not classical full penetrant monogenic). For example, deletion of one SLC9A3allele plus a CFTR variant.