J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-63634 | DOI: 10.4274/jcrpe.galenos.2023.2023-5-2

Novel Variant of SLC34A3 in a Compound Heterozygous Brazilian Girl with Hereditary Hypophosphatemic Rickets with Hypercalciuria

Luciana Pinto Valadares¹, Daniel Rocha de Carvalho^2
1Unit of Osteometabolic Disorders, SARAH Network of Rehabilitation Hospitals, Brasília, Brazil
²Medical Genetics Unit, SARAH Network of Rehabilitation Hospitals, Brasília, Brazil.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare FGF23-independent disorder caused by biallelic variants in the SLC34A3 gene. The disease severity varies, and patients have an increased risk of developing renal complications. Phosphate supplementation is standard of care and active vitamin D analogs are not indicated as they could worsen the hypercalciuria. We report a Brazilian girl with HHRH who presented with knee pain and progressive genu valgum deformity that became apparent later in childhood (at age 8). Nephrocalcinosis was also identified at age 13. Next-generation sequencing (NGS) target panel directed to inherited forms of rickets detected compound heterozygous pathogenic variants in SLC34A3, including a novel missense variant c.1217G>T (p.Gly406Val). Compliance to oral phosphorus therapy was suboptimal and adjunctive chlorthalidone therapy improved hypercalciuria. Our case highlights the phenotypic variability of patients with HHRH and expands the growing list of SLC34A3 variants associated with this disorder. An accurate diagnosis is crucial for proper treatment, and a thiazide diuretic may be useful as adjunctive therapy for controlling hypercalciuria.

Keywords: hereditary hypophosphatemic rickets with hypercalciuria, SCL34A3 pathogenic variants, hypercalciuria

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