## Vitamin D-Dependent Rickets Type 1 (VDDR-1) ### Pathophysiology VDDR-1 is an autosomal recessive disorder caused by mutations in the **CYP27B1 gene**, which encodes the 1α-hydroxylase enzyme located in the proximal tubule of the kidney. ### Biochemical Cascade 1. **25-hydroxylation** (liver) → 25-hydroxyvitamin D [25(OH)D] — normal 2. **1α-hydroxylation** (kidney) → 1,25-dihydroxyvitamin D [1,25(OH)₂D] — **DEFECTIVE in VDDR-1** 3. 1,25(OH)₂D acts on VDR in intestine, bone, and kidney ### Key Laboratory Findings in VDDR-1 | Parameter | Finding | | --- | --- | | 25(OH)D | Normal or high | | 1,25(OH)₂D | **Low** | | PTH | Elevated (secondary hyperparathyroidism) | | Calcium | Low | | Phosphate | Low | | ALP | Elevated | **Key Point:** VDDR-1 presents with **low 1,25(OH)₂D despite normal 25(OH)D levels** — this distinguishes it from nutritional rickets (low 25(OH)D) and VDDR-2 (high 1,25(OH)₂D with VDR defect). ### Clinical Presentation - Onset: typically 6 months to 2 years - Severe rickets with hypocalcemia, seizures, tetany - Alopecia (hair loss) — characteristic feature - Responds to **high-dose calcitriol** (active vitamin D analog) **High-Yield:** The defect is in **kidney activation**, not hepatic synthesis or tissue receptor function. 
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.