Hypophosphatemic Rickets with Hypercalciuria: A Novel Homozygous Mutation in SLC34A3 and Literature Review

Objective Hypophosphatemic rickets with hypercalciuria (HHRH) is a rare, recessively-inherited form of rickets caused by homozygous or compound heterozygous mutations in the SLC34A3 gene that encodes the renal tubular phosphate transporter protein NaPi2c. The bone phenotype varies from severe rickets to no disease. Accurate diagnosis is important as the treatment differs from other forms of rickets. Methods The patient was a 12-year-old boy from the Indian subcontinent with florid hypophosphatemic rickets. A targeted gene panel to search for mutations in genes associated with inherited forms of rickets was performed. We also completed a literature search of published cases of HHRH. Results The targeted gene panel demonstrated a novel homozygous SLC34A3 mutation: c.1339 G>A (p.Ala447Thr). His parents were heterozygous for the mutation. In our literature review we found that people with homozygous SLC34A3 mutations were more likely to have rickets than those with compound heterozygous mutations (85% versus 45%, p<0.002) and that serum phosphate z scores were lower in those with rickets than those without (-3.3 with a standard deviation of 1.5 versus -2.1 with a standard deviation of 1.5, p<0.005). Conclusion The bone phenotype of HHRH is related to the nature of the mutation and serum phosphate levels. Targeted gene panels can aid in the accurate diagnosis of inherited forms of rickets, and facilitate correct treatment.