Makindo Medical Notes

🧬 Menkes Disease (also known as “Kinky Hair Disease”) is a rare X-linked recessive disorder of copper metabolism. It results from mutations in the ATP7A gene 🧫, leading to defective intestinal absorption and cellular transport of copper. This causes systemic copper deficiency and defective connective tissue formation. 🔄 In contrast, Wilson Disease (ATP7B mutation) causes copper overload in tissues — the opposite biochemical problem. ⚖️

🧠 Pathophysiology

• 🔩 Copper is an essential cofactor for several enzymes (e.g. lysyl oxidase, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase).
• 🧬 The ATP7A gene encodes a copper-transporting ATPase located in the intestinal mucosa and across the blood-brain barrier.
• 🚫 Defective copper transport → systemic copper deficiency → ↓ activity of lysyl oxidase → impaired collagen and elastin cross-linking.
• 🩸 Results in weak connective tissues, brittle hair, neurological dysfunction, and vascular fragility.

🧩 Clinical Features

• 💇‍♂️ “Kinky,” brittle, depigmented hair: Pathognomonic finding — hair appears sparse, twisted, and steel-coloured due to keratin cross-link defects.
• 🐢 Developmental delay and hypotonia: Severe neurodegeneration, seizures, poor feeding, and muscle weakness usually appear in infancy.
• 📉 Growth failure: Poor weight gain and stunted linear growth despite adequate nutrition.
• 🧠 Cerebral and vascular abnormalities: Tortuous arteries and fragile vessels → cerebral aneurysms or intracranial haemorrhage.
• 🥶 Hypothermia: Impaired thermoregulation due to autonomic and metabolic dysfunction.
• 🦴 Connective tissue weakness: Skin laxity, skeletal fractures, and joint hypermobility may occur.

🧪 Diagnosis

• 🧫 Clinical recognition: Characteristic hair, facial features (sagging cheeks, large ears), and neurological decline in a male infant.
• 🩸 Biochemical tests: ↓ serum copper (<50 µg/dL) and ↓ ceruloplasmin (<20 mg/dL).
• 🧬 Genetic testing: Mutation in ATP7A confirms the diagnosis.
• 🔬 Hair microscopy: Shows “pili torti” — twisted hair shafts.
• 🧍 Skin biopsy: Abnormal collagen fibrils with decreased cross-linking.

💊 Management

• 💉 Parenteral copper supplementation: Early administration (preferably within first 2 months) of copper histidine or copper chloride can improve survival if started before neurological damage.
• 🧘‍♀️ Supportive therapy: Physiotherapy and occupational therapy for hypotonia and motor delay.
• 🧠 Neurological monitoring: Seizure control (e.g. with valproate or levetiracetam) and surveillance for vascular complications.
• 📆 Multidisciplinary care: Genetic counselling, nutritional support, and regular follow-up in a metabolic clinic.
• ⛔ Prognosis is poor if untreated — most affected infants die by age 3 due to neurological and vascular complications.

⚖️ Comparison: Menkes vs Wilson Disease

💡 Teaching Tip: Menkes = “Missing copper” 🧬 → connective tissue weakness and neurodegeneration. Wilson = “Too much copper” ⚗️ → liver and brain toxicity. Remember: ATP7A = Absorption, ATP7B = Biliary excretion. Early genetic testing in siblings is crucial for prevention and counselling. 👨‍👩‍👧‍👦