MCAD deficiency is a common autosomal recessive fatty acid oxidation disorder caused by deficiency of the medium-chain acyl-CoA dehydrogenase enzyme. This impairs the body’s ability to generate energy from medium-chain fatty acids during fasting, leading to hypoketotic hypoglycaemia and risk of sudden metabolic collapse.

🧠 Pathophysiology (Exam Gold)

🔋 Normally, fatty acids are broken down via β-oxidation to produce energy during fasting
❌ MCAD deficiency blocks oxidation of medium-chain fatty acids
⬇️ Reduced ketone production → brain lacks alternative fuel
⬇️ Reduced glucose production → hypoglycaemia
🧪 Accumulation of fatty acid intermediates → toxicity

⚠️ Clinical Presentation

👶 Often presents in infancy or early childhood
⏳ Triggered by fasting, illness, or vomiting
🧠 Lethargy, drowsiness, confusion
⚡ Seizures or coma
🚫 No preceding warning signs in some cases → sudden collapse

🚨 Hallmark Feature

🍬 Hypoglycaemia WITHOUT ketosis (very high-yield exam clue)

🧪 Investigations

🍬 Low blood glucose
🚫 Low or absent ketones
🧴 Acylcarnitine profile – elevated medium-chain species (e.g. C8)
🧪 Urine organic acids – dicarboxylic acids
🧬 Genetic testing confirms diagnosis

💊 Emergency Management

🍬 Immediate IV glucose (key lifesaving step)
🚫 Avoid fasting
💧 IV fluids and supportive care
⚠️ Treat promptly to prevent brain injury

🥗 Long-Term Management

🍽️ Avoid prolonged fasting (critical)
🍬 Regular carbohydrate intake
📋 Emergency “sick day” plan (increase glucose intake during illness)
👨‍👩‍👧 Family education is essential

👶 Newborn Screening (UK Context)

🧪 Included in heel prick test (day 5)
🎯 Early detection prevents sudden death

💡 Exam & Clinical Tips

🍬 Hypoglycaemia + low ketones = fatty acid oxidation defect
⚠️ Collapse after fasting or minor illness is a key clue
🚫 Giving glucose is both diagnostic and therapeutic
🧠 One of the most important preventable causes of sudden death in children

From a clinical reasoning perspective, MCAD deficiency represents a failure of the body’s metabolic backup system. When glycogen stores are depleted during fasting, the body normally switches to fatty acid oxidation to generate ketones as an alternative brain fuel. In MCAD deficiency, this switch fails, leaving the brain dependent on rapidly falling glucose levels, resulting in hypoketotic hypoglycaemia. In UK practice, early identification via newborn screening and strict avoidance of fasting dramatically improves prognosis and prevents catastrophic presentations.

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MCAD Deficiency (Medium-Chain Acyl-CoA Dehydrogenase Deficiency)