Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy.

Abstract

Introduction: Hereditary vitamin D resistant rickets (HVDRR) is a rare autosomal recessive disorder marked by end-organ resistance of 1,25-dihydroxyvitamin D secondary to various mutations in the vitamin D receptor gene. The currently accepted treatment modality involves bypassing the affected receptors in the gut with high-dose intravenous calcium. In a few limited case reports, cinacalcet, a calcimimetic, has been used as an adjunctive therapy.

Material and methods: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation.

Results: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels.

Conclusions: This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.