Learning Objective: Explain the genetic defect, pathophysiology, clinical features, and key differentiating points of Menkes disease versus Wilson disease.
Overview
- Inheritance: X-linked recessive
- Primary Defect: Impaired copper absorption and transport
- Gene Affected: ATP7A (contrast with ATP7B in Wilson disease)
- Result: Copper deficiency → ↓ activity of copper-dependent enzymes (e.g., lysyl oxidase) → defective collagen cross-linking
Pathophysiology
| Step |
Mechanism |
| Genetic defect |
A mutation in ATP7A, causing defective copper transport |
| Copper status |
Systemic copper deficiency (unlike Wilson disease, which causes copper accumulation) |
| Enzyme effect |
↓ Lysyl oxidase activity → impaired collagen cross-linking |
| Tissue consequences |
Weak connective tissue, vascular fragility, abnormal hair structure |
Clinical Features
| System |
Manifestations |
| Hair |
Brittle, “kinky” or “steely” hair |
| Growth & Development |
Growth retardation, developmental delay |
| Musculoskeletal |
Hypotonia, joint laxity |
| Vascular |
↑ risk of cerebral aneurysms, arterial tortuosity |
| Other |
Fairly distinct facial features (pale skin, sagging cheeks) |
Key Comparisons: Menkes vs Wilson Disease
| Feature |
Menkes Disease |
Wilson Disease |
| Gene |
ATP7A |
ATP7B |
| Copper |
↓ Absorption → systemic deficiency |
↓ Excretion → copper buildup |
| Lysyl oxidase |
↓ activity → defective collagen |
Normal |
| Clinical hallmark |
Kinky hair, growth/development delay |
Kayser-Fleischer rings, liver disease, and neurologic signs |
Key Points
- Menkes disease: X-linked, copper deficiency, defective collagen → “kinky hair,” hypotonia, aneurysms
- Wilson disease: Autosomal recessive, copper excess, liver and neurological involvement
- Copper is a cofactor for lysyl oxidase → cross-linking of collagen critical for connective tissue integrity
Activity
