Abstract
Background
Mutations in SLC34A1 and SLC34A2 genes, which encode co-transporters NaPi2a and NaPi2c, respectively, can lead hypophosphatemia due to renal phosphate loss. This condition results in hypercalcitriolemia and hypercalciuria, leading formation of kidney stones and nephrocalcinosis. Phenotype is highly variable. Management include hyperhydration, dietary modifications, and/or phosphate supplementation. Thiazides and azoles may be used, but randomized studies are needed to confirm their clinical efficacy.
Methods
We conducted a retrospective study in pediatric nephrology unit at Grenoble University Hospital from January 2010 to December 2023. Study aimed to describe clinical and biological symptoms of patients with confirmed SLC34A1 and SLC34A3 gene mutations and their outcomes.
Results
A total of 11 patients (9 females) from 6 different families had mutations in the SLC34A1 (5 patients) and SLC34A3 (6 patients) genes. Median age at diagnosis was 72 [1-108] months. Average follow-up duration was 8.1 ± 4.5 years. Presenting symptom was nephrocalcinosis (4 cases), followed by renal colic (3 cases). At diagnosis, 90% of patients had hypercalciuria and 45% had hypercalcitriolemia. Management included hyperhydration and dietary advice. All patients showed favorable outcomes with normal growth and school attendance. One patient with an SLC34A3 mutation showed regression of nephrocalcinosis. Renal function remained normal.
Conclusion
Clinical and biological manifestations of SLC34 gene mutations are highly variable, even among siblings; therefore, management must be personalized. Hygienic-dietary measures (such as hyperhydration, a low sodium diet, and age-appropriate calcium intake) result in favorable outcomes in most cases. Use of azoles (e.g., fluconazole) appears to be a promising therapeutic option.