Association between compound heterozygous mutations of SLC34A3 and hypercalciuria

Area of Science:

• Genetics
• Nephrology
• Endocrinology

Background:

• Mutations in the SLC34A3 gene are known to cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH).
• Typically, patients with compound heterozygous or homozygous SLC34A3 mutations exhibit skeletal lesions alongside hypercalciuria, hypophosphatemia, and elevated 1,25-dihydroxy vitamin D levels.

Observation:

• A 3-year-old girl presented with microscopic hematuria, elevated 1,25-dihydroxy vitamin D, hypercalciuria, and reduced serum inorganic phosphorus.
• Despite findings consistent with HHRH, including bilateral nephrocalcinosis, the patient lacked skeletal lesions and a family history of bone disease.
• Genetic analysis identified compound heterozygous mutations (c.175+1 G>A and c.1234 C>T) in the SLC34A3 gene.

Findings:

• This case demonstrates that biallelic SLC34A3 mutations can lead to hypercalciuria without the development of rickets.
• The patient's presentation highlights a variant phenotype of SLC34A3-associated disorders.

Implications:

• SLC34A3 mutations should be considered in the differential diagnosis of hypercalciuria of unknown origin, even in the absence of skeletal abnormalities.
• Oral inorganic phosphate administration is a potential therapeutic strategy for such patients.
• Further research into the genotype-phenotype correlations of SLC34A3 mutations is warranted.