In vitamin D-dependent rickets type 1 (VDDR1), which enzyme is deficient?

Explanation

## Vitamin D-Dependent Rickets Type 1 (VDDR1) **Key Point:** VDDR1 is an autosomal recessive disorder caused by deficiency of **renal 1α-hydroxylase**, the enzyme that converts 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D. ### Vitamin D Activation Pathway ```mermaid flowchart LR A["7-Dehydrocholesterol<br/>(Skin)"] -->|UV-B| B["Vitamin D3<br/>(Cholecalciferol)"] B --> C["25-Hydroxyvitamin D<br/>(Calcidiol)<br/>Liver"] C -->|1α-Hydroxylase<br/>KIDNEY| D["1,25-Dihydroxyvitamin D<br/>(Calcitriol)<br/>ACTIVE FORM"] C -->|24-Hydroxylase<br/>KIDNEY| E["24,25-Dihydroxyvitamin D<br/>INACTIVE"] D --> F["Intestinal Ca²⁺ absorption<br/>Bone mineralization"] style D fill:#ff6b6b style C fill:#ffd93d ``` ### Biochemical Pattern in VDDR1 | Parameter | Finding | Explanation | |-----------|---------|-------------| | 25-OH vitamin D | **Normal/Elevated** | Liver function intact | | 1,25-OH vitamin D | **LOW** | Enzyme deficiency | | PTH | Elevated | Secondary hyperparathyroidism | | Serum calcium | Low | Impaired GI absorption | | Serum phosphate | Low | PTH-mediated renal wasting | | Alkaline phosphatase | Elevated | Increased bone turnover | **High-Yield:** VDDR1 is distinguished from nutritional rickets by **normal or elevated 25-hydroxyvitamin D** despite severe rickets. This is the diagnostic clue—rickets with normal vitamin D levels suggests a genetic defect in vitamin D metabolism, not dietary deficiency. **Clinical Pearl:** VDDR1 responds dramatically to **high-dose calcitriol (1,25-dihydroxyvitamin D)** supplementation, bypassing the defective enzyme. This is the treatment of choice and confirms the diagnosis. **Mnemonic:** **1α-OH** = **1-alpha hydroxylase** (kidney) is deficient in VDDR1. The "1" in the enzyme name matches the "1" in VDDR**1**.