Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c
Abstract
Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)2D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)2D synthesis via increased PTH production.
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BibTeX
@article{brunkhorst2026presentation,
title = {{Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c}},
author = {Max Brunkhorst and Lena Brunkhorst and Helge Martens and Svetlana Papizh and Martine Besouw and Corinna Grasemann and Serap Turan and Przemyslaw Sikora and Milan Chromek and Elisabeth Cornelissen and Marc Fila and Marc Lilien and Jeremy Allgrove and Thomas J. Neuhaus and Mehmet Eltan and Laura Espinosa and Dirk Schnabel and Ibrahim Gokce and Juan David González-Rodríguez and Priyanka Khandelwal and Mandy G. Keijzer-Veen and Felix Lechner and Maria Szczepańska and Marcin Zaniew and Justine Bacchetta and Francesco Emma and Dieter Haffner},
journal = {Kidney International},
year = {2026},
month = sep,
doi = {10.1016/j.kint.2024.08.035},
url = {https://hal.science/hal-05025808v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c
AU - Max Brunkhorst
AU - Lena Brunkhorst
AU - Helge Martens
AU - Svetlana Papizh
AU - Martine Besouw
AU - Corinna Grasemann
AU - Serap Turan
AU - Przemyslaw Sikora
AU - Milan Chromek
AU - Elisabeth Cornelissen
AU - Marc Fila
AU - Marc Lilien
AU - Jeremy Allgrove
AU - Thomas J. Neuhaus
AU - Mehmet Eltan
AU - Laura Espinosa
AU - Dirk Schnabel
AU - Ibrahim Gokce
AU - Juan David González-Rodríguez
AU - Priyanka Khandelwal
AU - Mandy G. Keijzer-Veen
AU - Felix Lechner
AU - Maria Szczepańska
AU - Marcin Zaniew
AU - Justine Bacchetta
AU - Francesco Emma
AU - Dieter Haffner
PY - 2026
DA - 2026/09/02
JO - Kidney International
DO - 10.1016/j.kint.2024.08.035
UR - https://hal.science/hal-05025808v1
AB - Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)2D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)2D synthesis via increased PTH production.
SN - 0085-2538
SN - 1523-1755
ER -