Clinical Phenotype in a Toddler with a Novel Heterozygous Mutation of the Vitamin D Receptor

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Vitamin D-resistant rickets (VDRR) is a rare genetic disorder characterized by impaired phosphate reabsorption and bone mineralization.
• Genetic defects in the vitamin D receptor (VDR) are a known cause of VDRR, leading to impaired vitamin D signaling.

Observation:

• A toddler presented with severe VDRR, exhibiting extremely high alkaline phosphatase and parathyroid hormone (PTH) levels, indicative of significant bone metabolic disturbance.
• Genetic analysis revealed novel compound heterozygous mutations within the ligand-binding domain of the VDR gene.

Findings:

• The identified VDR mutations represent a new cause of VDRR, affecting the critical ligand-binding site.
• The patient demonstrated a remarkable clinical and biochemical improvement with calcitriol (1,25(OH)2D) therapy, suggesting preserved downstream signaling pathways.

Implications:

• This case expands the known spectrum of VDR mutations causing VDRR.
• Early diagnosis and targeted calcitriol therapy can be highly effective in managing VDRR caused by VDR ligand-binding site mutations.
• Understanding these novel mutations provides insights into VDR function and VDRR pathogenesis.