Composite Phenotype: Recurrent Nephrolithiasis and Chronic Kidney Disease in an Adult with Biallelic <italic>SLC34A3</italic> and Monoallelic <italic>SLC3A1</italic> Pathogenic Variants - Who Is "The Culprit"?

introductionKidney stones are common and can arise from many etiologies including genetic and environmental. Biallelic pathogenic variants in the solute carrier family 34-member 3 (SLC34A3) gene cause hereditary hypophosphatemic rickets with hypercalciuria, while both monallaelic and biallelic pathogenic variants in SLC3A1 cause cystinuria. CASE PRESENTATION: We studied a 29-year-old man, who has a personal history of recurrent nephrolithiasis (with over 10 kidney stone episodes requiring lithotripsy and surgical interventions), medullary nephrocalcinosis, pyelonephritis, bilateral septate renal cysts, and chronic kidney disease. Genetic testing showed compound heterozygous pathogenic variants in SLC34A3 [NM_001177316.2, c.448+1G>A and c.575C>T (p.Ser192Leu)) and a heterozygous pathogenic variant in SLC3A1 (gain of exons 5-9). The renal calculi mostly comprised; 50% calcium oxalate monohydrate, and 30% calcium phosphate (hydroxy- and carbonate-apatite) as well as 20% calcium oxalate dihydrate.

conclusionWe report the clinical phenotype of a patient with concomitant biallelic and monoallelic pathogenic variants in SLC34A3 and SLC3A1, respectively.