A child presents with a history of fractures, multiple petechiae, perifollicular hemorrhages, and gum bleeding. Which of the following enzyme defects is involved?

Explanation

## Correct Answer: B. Prolyl hydroxylase The clinical presentation—fractures, petechiae, perifollicular hemorrhages, and gum bleeding—is pathognomonic for **vitamin C deficiency (scurvy)**. Prolyl hydroxylase is a vitamin C–dependent enzyme essential for collagen cross-linking. Vitamin C (ascorbic acid) acts as a cofactor for prolyl and lysyl hydroxylases, which hydroxylate proline and lysine residues in procollagen. Without adequate hydroxylation, collagen cannot form stable triple helices or cross-links, resulting in defective connective tissue. This explains the bleeding gums (defective gingival collagen), petechiae and perifollicular hemorrhages (fragile blood vessel walls), and fractures (weak bone matrix). In India, scurvy is still encountered in malnourished children, particularly in urban slums and during monsoon seasons when fresh fruit availability is low. The defect is not in the enzyme itself but in its cofactor (vitamin C), making prolyl hydroxylase functionally inactive. This distinguishes scurvy from genetic collagen disorders like Ehlers–Danlos syndrome (lysyl oxidase defect) or osteogenesis imperfecta (type I collagen mutation). ## Why the other options are wrong **A. Alkaline phosphatase** — Alkaline phosphatase deficiency causes hypophosphatasia, characterized by defective bone mineralization, rickets-like features, and dental problems—but NOT the classic bleeding manifestations (petechiae, perifollicular hemorrhages, gum bleeding) seen in scurvy. Alkaline phosphatase is unrelated to collagen synthesis or vitamin C metabolism. **C. Tyrosinase** — Tyrosinase deficiency causes oculocutaneous albinism, presenting with hypopigmentation, photophobia, and visual problems—not fractures or hemorrhagic manifestations. Tyrosinase is involved in melanin synthesis, not collagen cross-linking or connective tissue integrity. **D. Lysyl oxidase** — Lysyl oxidase deficiency (Menkes disease or acquired copper deficiency) does cause connective tissue defects and can present with fractures and bleeding. However, the classic presentation includes kinky hair, neurological symptoms, and vascular tortuosity—not the perifollicular hemorrhages and gum bleeding characteristic of scurvy. Lysyl oxidase requires copper, not vitamin C, as its cofactor. ## High-Yield Facts - **Prolyl hydroxylase** requires **vitamin C** as a cofactor; deficiency causes scurvy with defective collagen cross-linking. - **Scurvy** presents with fractures, petechiae, perifollicular hemorrhages, bleeding gums, and poor wound healing due to weak connective tissue. - **Vitamin C deficiency** is still endemic in malnourished Indian children; diagnosis confirmed by plasma ascorbic acid <0.2 mg/dL. - **Collagen stabilization** requires hydroxylation of proline and lysine residues; without this, collagen triple helix formation fails. - **Perifollicular hemorrhages** (bleeding around hair follicles) are pathognomonic for scurvy and distinguish it from other bleeding disorders. ## Mnemonics **SCURVY Signs** **S**wollen gums, **C**ollagen defect, **U**nhealed wounds, **R**ash (perifollicular), **V**itamin C deficiency, **Y**ield to ascorbic acid. Use when recalling the clinical triad of bleeding gums + petechiae + fractures. **Vitamin C Enzymes** **Pro-Lys Hydroxylases** (Prolyl & Lysyl) need **Vitamin C**. Both are collagen-stabilizing enzymes; remember 'Pro-Lys' as the two hydroxylases that require ascorbic acid as cofactor. ## NBE Trap NBE pairs lysyl oxidase (option D) with connective tissue defects to trap students who confuse Menkes disease (copper deficiency) with scurvy (vitamin C deficiency). Both cause bleeding and fractures, but the perifollicular hemorrhages and gum bleeding are specific to scurvy. ## Clinical Pearl In Indian pediatric practice, scurvy is often missed in malnourished children presenting with recurrent infections and poor growth. The combination of bleeding gums + perifollicular hemorrhages should immediately trigger vitamin C supplementation (100–200 mg daily), with clinical improvement visible within 2–3 weeks—a diagnostic and therapeutic test. _Reference: Harper Biochemistry Ch. 49 (Collagen); KD Tripathi Pharmacology Ch. 42 (Vitamins); Robbins Pathology Ch. 9 (Nutritional Diseases)_