Max Brunkhorst, Lena Brunkhorst, Helge Martens, Svetlana Papizh, Martine Besouw, Corinna Grasemann, Serap Turan, Przemyslaw Sikora, Milan Chromek, Elisabeth Cornelissen, Marc Fila, Marc Lilien, Jeremy Allgrove, Thomas J Neuhaus, Mehmet Eltan, Laura Espinosa, Dirk Schnabel, Ibrahim Gokce, Juan David González-Rodríguez, Priyanka Khandelwal, Mandy G Keijzer-Veen, Felix Lechner, Maria Szczepańska, Marcin Zaniew, Justine Bacchetta, Francesco Emma, Dieter Haffner
{"title":"Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c.","authors":"Max Brunkhorst, Lena Brunkhorst, Helge Martens, Svetlana Papizh, Martine Besouw, Corinna Grasemann, Serap Turan, Przemyslaw Sikora, Milan Chromek, Elisabeth Cornelissen, Marc Fila, Marc Lilien, Jeremy Allgrove, Thomas J Neuhaus, Mehmet Eltan, Laura Espinosa, Dirk Schnabel, Ibrahim Gokce, Juan David González-Rodríguez, Priyanka Khandelwal, Mandy G Keijzer-Veen, Felix Lechner, Maria Szczepańska, Marcin Zaniew, Justine Bacchetta, Francesco Emma, Dieter Haffner","doi":"10.1016/j.kint.2024.08.035","DOIUrl":null,"url":null,"abstract":"<p><p>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)<sub>2</sub>D 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)<sub>2</sub>D 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)<sub>2</sub>D synthesis via increased PTH production.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney international","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.kint.2024.08.035","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Kidney International (KI), the official journal of the International Society of Nephrology, is led by Dr. Pierre Ronco (Paris, France) and stands as one of nephrology's most cited and esteemed publications worldwide.
KI provides exceptional benefits for both readers and authors, featuring highly cited original articles, focused reviews, cutting-edge imaging techniques, and lively discussions on controversial topics.
The journal is dedicated to kidney research, serving researchers, clinical investigators, and practicing nephrologists.