## Vitamin D-Dependent Rickets Type 1 (VDDR1) ### Enzymatic Defect **Key Point:** VDDR1 is caused by deficiency of **1α-hydroxylase**, the enzyme responsible for converting 25-hydroxyvitamin D [25(OH)D] to the active form 1,25-dihydroxyvitamin D [1,25(OH)~2~D] in the proximal tubule of the kidney. ### Biochemical Profile | Parameter | Finding | | --- | --- | | 25(OH)D | Normal or elevated | | 1,25(OH)~2~D | **Low** | | Serum calcium | Low | | Serum phosphate | Low | | PTH | Elevated (secondary hyperparathyroidism) | | ALP | Elevated | ### Clinical Features - Presents in infancy (3–6 months) - Severe rickets with hypocalcemic seizures - Alopecia (hair loss) is a characteristic feature - Responds dramatically to **calcitriol (1,25(OH)~2~D~3~) supplementation** **High-Yield:** The hallmark of VDDR1 is the **dissociation between normal/high 25(OH)D and low 1,25(OH)~2~D** — this distinguishes it from nutritional rickets (both are low) and VDDR2 (receptor defect). ### Inheritance Autosomal recessive; mutations in *CYP27B1* gene encoding 1α-hydroxylase. **Clinical Pearl:** Unlike nutritional rickets, VDDR1 does NOT respond to high-dose vitamin D~2~ or D~3~; it requires active metabolite (calcitriol) therapy. 
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