Variable Clinical Presentation of Children with Hereditary Hypophosphatemic Rickets with Hypercalciuria: A Case Series and Review of the Literature

Horm Res Paediatr. 2021;94(9-10):374-389. doi: 10.1159/000520299. Epub 2021 Oct 19.

Abstract

Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare condition of renal phosphate wasting due to SLC34A3 mutations [Am J Hum Genet. 2006;78(2):193-201]. Patients exhibit low serum phosphorus, high 1,25-dihydroxyvitamin D, and inappropriately high urine phosphate and calcium. However, symptoms vary, and little is known about specific phenotype-genotype correlations.

Methods: We report 3 HHRH cases in unrelated 12-year-old, 9-year-old, and 14-year-old patients and perform a systematic literature review.

Results: All 3 patients exhibited labs typical of HHRH. Yet, their presentations differed, and 2 novel SLC34A3 variants were identified. As found in the literature review, bone symptoms are most common (50%), followed by renal symptoms (17%), combined bone and renal symptoms (18%), and asymptomatic (9%).

Conclusion: These 3 cases highlight the variability of presenting signs and symptoms among individuals with HHRH. An accurate diagnosis is critical as treatment differs from other disorders of phosphate wasting, urinary stones, and mineralization defects.

Keywords: Hereditary hypophosphatemic rickets with hypercalciuria; Pediatric endocrinology; Pediatric nephrology; Phosphate metabolism; Vitamin D.

Publication types

  • Case Reports
  • Systematic Review

MeSH terms

  • Familial Hypophosphatemic Rickets* / complications
  • Familial Hypophosphatemic Rickets* / diagnosis
  • Familial Hypophosphatemic Rickets* / genetics
  • Humans
  • Hypercalciuria / diagnosis
  • Hypercalciuria / drug therapy
  • Hypercalciuria / genetics
  • Mutation
  • Phosphates
  • Rickets* / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIc / genetics

Substances

  • Phosphates
  • Sodium-Phosphate Cotransporter Proteins, Type IIc