A 2-year-old boy presents with bowing of legs, delayed fontanelle closure, and hypocalcemic seizures. Regarding vitamin D deficiency rickets in children, all of the following are correct EXCEPT:

Explanation

## Vitamin D — Nature, Metabolism, and Deficiency Rickets ### Chemical Classification **Key Point:** Vitamin D is a **fat-soluble steroid hormone**, NOT water-soluble. It is synthesized in the skin (7-dehydrocholesterol → previtamin D → vitamin D₃) and stored in adipose tissue and liver. ### Metabolism and Activation ```mermaid flowchart TD A[Skin: 7-dehydrocholesterol + UVB]:::action --> B[Previtamin D₃] B --> C[Vitamin D₃ circulates to liver] C --> D[Liver: 25-hydroxylase converts to 25-OH-D]:::action D --> E[25-OH-D: Storage form, indicator of vitamin D status] E --> F[Kidney: 1α-hydroxylase converts to 1,25-OH-D]:::action F --> G[1,25-OH-D: Active form, binds VDR]:::outcome G --> H[Intestinal calcium/phosphate absorption] G --> I[Bone mineralization] G --> J[PTH suppression] ``` ### Biochemical Actions of Calcitriol (1,25-OH-D) 1. **Intestinal absorption:** Increases expression of calbindin-D and Ca²⁺-ATPase → enhanced Ca²⁺ and PO₄³⁻ absorption 2. **Bone:** Facilitates mineralization; mobilizes calcium in severe deficiency 3. **PTH regulation:** Suppresses PTH synthesis and secretion (negative feedback) 4. **Renal tubule:** Increases calcium reabsorption in distal tubule ### Pathophysiology of Nutritional Rickets | Stage | Mechanism | Biochemical Changes | |-------|-----------|--------------------| | Early | ↓ 25-OH-D → ↓ Ca²⁺ absorption | ↑ PTH, normal/low Ca²⁺, normal PO₄³⁻ | | Progressive | ↑ PTH → ↑ urinary PO₄³⁻ wasting | ↑ ALP, ↑ PTH, ↓ PO₄³⁻, ↓ Ca²⁺ | | Severe | Hypocalcemia → seizures, tetany | ↓ Ca²⁺, ↓ PO₄³⁻, ↑ ALP, ↑ PTH | **High-Yield:** Secondary hyperparathyroidism in rickets causes increased renal phosphate wasting (via FGF23 and PTH), resulting in hypophosphatemia. ### Clinical Features of Rickets - **Skeletal:** Bowing of legs, frontal bossing, rachitic rosary, delayed epiphyseal closure - **Dental:** Delayed tooth eruption, enamel hypoplasia - **Metabolic:** Hypocalcemia → seizures, tetany, laryngospasm - **Growth:** Failure to thrive, delayed motor milestones **Clinical Pearl:** In India, nutritional rickets is common due to limited sun exposure (veiling, indoor lifestyle), dietary restrictions (vegetarian diets low in vitamin D), and malabsorption. Diagnosis: serum 25-OH-D <20 ng/mL (deficiency), <30 ng/mL (insufficiency). **Warning:** Do NOT confuse vitamin D (fat-soluble) with B vitamins (water-soluble). Vitamin D is stored in body tissues; water-soluble vitamins are not. [cite:Park 26e Ch 7; Harrison 21e Ch 95]