Vitamin D-Dependent Rickets Type 3: A Case Report and Systematic Review

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Rickets is commonly caused by vitamin D deficiency.
• Genetic mutations can lead to rare forms of rickets, including Vitamin D-Dependent Rickets (VDDR).
• Vitamin D-Dependent Rickets type 3 (VDDR3) was recently identified, linked to CYP3A4 gene mutations causing accelerated vitamin D inactivation.

Observation:

• This report details the third case of VDDR3 in a 2-year-old boy presenting with bone deformities and poor growth.
• The patient had no family history of rickets, suggesting a de novo mutation.
• Metabolic studies confirmed rapid inactivation of 25(OH)D and 1,25(OH)2D after cholecalciferol administration.

Findings:

• The patient's VDDR3 was caused by the same recurrent missense mutation in the CYP3A4 gene previously reported.
• Accelerated inactivation of key vitamin D metabolites (25(OH)D and 1,25(OH)2D) was confirmed.
• Treatment with high-dose daily cholecalciferol (10,000 IU) led to significant improvements.

Implications:

• This case underscores the importance of recognizing rare genetic causes of rickets.
• Precision therapy tailored to the specific genetic defect is vital for effective treatment.
• Early diagnosis and intervention can significantly improve growth and bone health in patients with VDDR3.