Pediatrics · Year 3 · from Pediatrics

Case 2: Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency

Patient Demographics

  • Age: 8-month-old male
  • Sex: Male

Chief Complaint

"He won't wake up after being sick."

History of Present Illness

An 8-month-old previously healthy boy is brought to the emergency department after his parents found him unresponsive in his crib this morning. He has had a viral illness with decreased oral intake and vomiting for the past 2 days. Last night he ate poorly and went to bed at 7 PM. His parents checked on him at 6 AM and found him limp and difficult to arouse. He has been exclusively breastfed and is just starting solids. Family history reveals that a maternal male cousin died unexpectedly at 11 months of age during a "stomach flu."

Physical Examination

  • Vital Signs: Temperature 37.8C, HR 180 bpm, RR 10/min (slow), BP 75/50 mmHg, SpO2 94% on room air, Glucose by fingerstick: 22 mg/dL
  • General: Lethargic, minimally responsive to painful stimuli
  • HEENT: Dry mucous membranes
  • Cardiovascular: Tachycardic, weak pulses
  • Respiratory: Slow, shallow breathing
  • Abdomen: Liver edge palpable 3 cm below costal margin
  • Neurologic: GCS 8 (E2V2M4), hypotonic, sluggish pupils

Laboratory Findings

  • Glucose: 18 mg/dL (critically low)
  • Venous blood gas: pH 7.28, pCO2 35, HCO3 16 (mild metabolic acidosis)
  • Urine ketones: Trace (inappropriately low - should be elevated with hypoglycemia)
  • Ammonia: 125 umol/L (elevated; normal <50)
  • Liver function tests: AST 450, ALT 380 (elevated)
  • Acylcarnitine profile (newborn screen was reportedly normal, but sample was collected at 20 hours of life): Elevated octanoylcarnitine (C8) - DIAGNOSTIC
  • Urine organic acids: Dicarboxylic aciduria

Diagnosis

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency with metabolic crisis

Clinical Reasoning

This infant presents with the classic MCAD deficiency crisis: hypoketotic hypoglycemia (severe hypoglycemia with inappropriately low ketones) triggered by fasting during illness. Key features include:

  • Fasting stress: Viral illness with poor intake for >12 hours (the overnight fast)
  • Hypoketotic hypoglycemia: Glucose 18 mg/dL with only trace ketones (in normal fatty acid oxidation, prolonged fasting produces ketones; in MCAD, medium-chain fatty acids cannot be oxidized)
  • Hepatomegaly and elevated transaminases: From fatty acid accumulation in liver
  • Encephalopathy: From hypoglycemia and toxic metabolite accumulation
  • Family history: Unexplained infant death (likely undiagnosed MCAD)
  • Diagnostic: Elevated C8 (octanoylcarnitine) on acylcarnitine profile

The newborn screen may have been falsely negative due to early collection (metabolic derangements may not be apparent at 20 hours).

Management

Acute Management:

  1. IV dextrose IMMEDIATELY:
  • D10W bolus: 2-4 mL/kg IV (target glucose >70 mg/dL)
  • Then D10W at 1.5x maintenance to maintain anabolism and prevent catabolism
  1. Goal glucose: Maintain 70-120 mg/dL
  2. Avoid lipid infusions: Contraindicated (cannot metabolize medium-chain fats)
  3. Monitoring: Glucose every 1-2 hours initially
  4. Treat underlying infection: Supportive care for viral illness

Long-Term Management:

  1. Avoid fasting:
  • Infants: No longer than 4-6 hours without feeding
  • Toddlers: No longer than 8-10 hours
  • Older children: No longer than 10-12 hours
  1. Sick day protocol:
  • Frequent high-carbohydrate feeds during illness
  • Low threshold for IV dextrose if cannot maintain oral intake
  • Emergency letter for ER visits
  1. L-carnitine supplementation: Consider based on carnitine levels
  2. Genetics referral: Confirm diagnosis, family counseling, sibling screening
  3. Medical alert bracelet: Essential

Prognosis

With early diagnosis and fasting avoidance, children with MCAD deficiency have excellent outcomes and normal development. Without diagnosis, mortality rate during crises is 20-25%.

Clinical Image

Image Description: Tandem mass spectrometry acylcarnitine profile demonstrating elevated octanoylcarnitine (C8), the biochemical hallmark of MCAD deficiency.

Source: Wikimedia Commons - Metabolic Screening URL: https://commons.wikimedia.org/wiki/File:Mass_spectrometry.svg License: CC BY-SA 4.0

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