Abstract: PO1363
Infantile Hypercalcemia Associated with a Novel Homozygous Mutation in SLC34A1 Gene Encoding Sodium-Dependent Phosphate Transporter 2A
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - II
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Hassanein, Mohamed, Cleveland Clinic, Cleveland, Ohio, United States
- Yahr, Jordana, Cleveland Clinic, Cleveland, Ohio, United States
- Roberts, Mary-Beth, Cleveland Clinic, Cleveland, Ohio, United States
- Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States
Introduction
Early-onset and familial hypercalcemia often suggest a genetic etiology which is rare. Infantile hypercalcemia (IH) is a rare, autosomal recessive disorder that occurs due to mutations in the SLC34A1 gene which encodes a sodium-dependent phosphate transporter 2A(NaPi-IIA) responsible for phosphate reabsorption in the kidney. We report an adult case who carried a clinical diagnosis of familial hypocalciuric hypercalcemia (FHH) since infancy, which is usually a benign condition characterized by autosomal dominant inheritance caused by mutations in calcium-sensing receptor (CASR) gene, while recently uncovered as IH related to a novel homozygous mutation in the SLC34A1 gene.
Case Description
A 36-year-old Finnish male with a diagnosis of FHH presented to the genetics nephrology clinic for consultation regarding the recurrence risk for his children. He was diagnosed with FHH during infancy in Finland and has been treated with a low calcium diet. Family history was notable for a clinical diagnosis of FHH in his older sister. Physical exam was unremarkable. Labs showed mild hypophosphatemia and decreased glomerular filtration rate (69 mL/min/1.73m2), with normal serum ionized calcium and intact parathyroid hormone. Twenty-four hour urine analysis revealed hypercalciuria 363 mg/d (normal <250), hypernatriuria 155 mmol/d (normal 50 – 150) and hypocitraturia 420 mg/d (normal >450). Kidney ultrasound showed bilateral medullary nephrocalcinosis. Genetic testing identified a novel homozygous variant in SLC34A1 gene (c.1483C>T) and was negative in CASR gene. Family genetic studies revealed his affected sister is also homozygous for the same variant while his unaffected sister is only a carrier. With the new diagnosis, he was started on potassium citrate and chlorthalidone, and was reassured with the low recurrence risk for his children.
Discussion
Mutations in the SLC34A1 gene lead to altered NaPi-IIA expression and reduced phosphate reabsorption, leading to hypophosphatemia. Secondary vitamin D activation leads to hypercalcemia, hypercalciuria, and nephrocalcinosis. We identified a novel mutation in the SLC34A1 gene which broadens the genetic spectrum of IH. This case highlights the importance of early genetic testing for suspected hereditary hypercalcemia that may help improve its diagnosis and treatment.