Akademik Veri Yönetim Sistemi
Calcified Tissue International, cilt.117, sa.1, 2026 (SCI-Expanded, Scopus)
Pathogenic variants in the SLC34A1 gene, which encodes the sodium-phosphate cotransporter NaPi-IIa, lead to a spectrum of renal tubular disorders, including infantile hypercalcemia type 2, nephrolithiasis/osteoporosis-hypophosphatemia type 2, and Fanconi renotubular syndrome type 2. Despite increasing recognition of SLC34A1-related disorders, data on genotype–phenotype correlations and treatment response remain limited due to the rarity of the condition. We retrospectively analyzed the clinical, biochemical, and molecular features of 11 patients from unrelated families carrying 12 pathogenic or likely pathogenic SLC34A1 variants, three of which were novel. Next-generation sequencing and ACMG-AMP criteria were used for variant classification. Biochemical parameters including serum phosphate, calcium, parathyroid hormone, urinary calcium, and TmP/GFR were evaluated. Treatment response to oral phosphate supplementation was longitudinally assessed. All patients exhibited hypercalciuria and nephrocalcinosis at diagnosis. Oral phosphate supplementation (5–20 mg/kg/day) resulted in normalization of urinary calcium excretion in 10 of 11 cases, regardless of baseline serum phosphate status. Linear growth improved in all but one patient. The identified mutations clustered primarily within functional domains of the NaPi-IIa protein, particularly amino acid residues 109–205 and 375–487. Several splice-site and codon-specific variants—such as those affecting Gly153 and Gly194—were highlighted as potential pathogenic hotspots. Our findings expand the mutational and phenotypic spectrum of SLC34A1-related disease and reinforce the utility of oral phosphate supplementation in managing hypercalciuria and promoting growth. Functional domain mapping and variant clustering analyses enhance understanding of disease mechanisms and support the importance of early diagnosis and long-term surveillance.