ESPE Abstracts

SLC34A1 gene encodes for the sodium-phosphate cotransporter 2A (NPT2a), highly expressed in the proximal renal tubule. Three different human phenotypes have been linked with NaPi-IIa variation: Hypophosphatemic Nephrolithiasis with Osteoporosis, Renotubular Fanconi Syndrome Type 2 and Infantile Hypercalcemia 2 (HCINF2). Dysfunctional NPT2a can lead to renal phosphate loss, hypophosphatemia, increased CYP27B, decreased CYP24A1 expression with increased 1,25(OH)2D and suppressed PTH. An IVF with donated oocyte 34 Wk SGA/IUGR girl, was diagnosed in the NICU with hypercalcemia 13.2 mg/dl and grade 3 nephrocalcinosis. Neonatal formula with no added vitamin D was advised. Serum P and P fractional excretion were high normal 5.1 mg/dl and 13.3 %, with marked hypercalciuria (Ca/Cr > 1), suppressed PTH 3.84 pg/ml, and high 1,25(OH)2D 163 pg/ml with 25(OH)D 24 ng/ml. At the age of 4 months PTHrP was elevated 34.2 pg/ml (<13). An NGS nephrolithiasis panel revealed a combination of two heterozygous SLC34A1 variants in trans: the common (2.55% of European populations) in-frame deletion c.272_292del (p.Val91_Ala97del) and a missense variant of unknown significance c.713A>C (p.Glu238Ala), inherited from the girl’s father. The second variant is absent from gnomAD (normal population database) and has been recorded as likely pathogenic in the ClinVar database. Initially a low calcium - no vitamin D formula was introduced (Calci-Lo XD, Abbott), previously proved efficient in published cases of SLC34A1 related disorders, resulting in serum Ca normalization (<10.5). However, 1,25(OH)2D remained abnormally high, and since vitamin D hypersensitivity was excluded, normalization of serum 25(OH)D (> 30 ng/ml) with cholecalciferol supplementation up to 1000 IU/day, resulted in a drop of 1,25(OH)2D at 99 pg/ml, restoration of suppressed PTH at 28 pg/ml, normalization of calciuria at 0.24, reduction of fractional P excretion at 8.27% and slightly improved renal radiologic image. Additionally, Bone Health Index, evaluated from a digital bone age X-ray (BoneXpert, Visiana, Denmark) at 8 months of age was in the highly osteopenic range -1.75 SDS (< -2 SDS, compatible with osteoporosis). Interestingly, FGF-23 remains inappropriately high-normal in this case of Infantile Hypercalcemia Type 2 (74 kRUL, 26-110), and this finding opens the discussion of a possible therapeutic trial with the specific FGF-23 monoclonal antibody blocker burosumab in selected SLC34A1 patients.