Overview
Definition:
Medium-chain acyl-CoA dehydrogenase (MCADD) deficiency is an autosomal recessive inherited disorder of fatty acid oxidation
It impairs the body's ability to break down medium-chain fatty acids for energy, particularly during periods of fasting or illness
The deficiency leads to the accumulation of medium-chain acylcarnitines and dicarboxylic acids, which can be toxic.
Epidemiology:
MCADD is one of the most common inherited disorders of fatty acid oxidation, with a prevalence estimated between 1 in 8,000 to 1 in 20,000 live births in populations of Northern European descent
Newborn screening programs have identified it as a significant cause of metabolic disease.
Clinical Significance:
Prompt recognition and management of MCADD are crucial to prevent severe metabolic decompensation, which can lead to hypoketotic hypoglycemia, liver dysfunction, encephalopathy, seizures, coma, and even sudden death
Understanding the emergency plan is vital for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Infants and young children typically present during an illness (e.g., viral gastroenteritis, upper respiratory infection) or prolonged fasting
Symptoms include: Acute onset of vomiting
Lethargy and somnolence
Poor feeding
Irritability
Fever
Seizures
Muscle weakness
Pallor
History of previous unexplained episodes of illness, vomiting, or lethargy may be present.
Signs:
Hypoglycemia (often severe and hypoketotic)
Hepatomegaly
Altered mental status (from drowsiness to coma)
Tachypnea
Tachycardia
Hypotension in severe cases
Signs of dehydration
Muscle hypotonia.
Diagnostic Criteria:
Diagnosis is typically suspected based on clinical presentation and confirmed by biochemical and genetic testing
Biochemical markers include: Hypoketotic hypoglycemia
Elevated very long-chain fatty acids (VLCFAs) in plasma
Elevated medium-chain acylcarnitines (especially C8, C10, C12) on acylcarnitine profile in blood or urine
Genetic testing for mutations in the ACADM gene confirms the diagnosis.
Emergency Management
Initial Management:
The primary goal is to correct hypoglycemia, provide calories, and remove toxic metabolites
Immediate interventions: Intravenous (IV) access
Administer IV glucose infusion: Start with a bolus of 10% glucose (2-4 ml/kg), followed by a continuous infusion of 10-15% glucose at a rate of 6-8 mg/kg/min to maintain normoglycemia
Avoid L-carnitine supplementation during the acute crisis unless severe deficiency is confirmed, as it may worsen outcome in some cases
Monitor urine for ketones and acylcarnitines.
Nutritional Support:
Provide adequate calories to prevent catabolism
For infants, breast milk or standard formula is usually sufficient if fed frequently
For older children, complex carbohydrates are preferred
Avoid prolonged fasting
If oral intake is not possible, maintain IV glucose infusion
Consider nasogastric (NG) tube feeding with carbohydrate-rich formula if the child is stable enough.
Medications:
Intravenous glucose is the cornerstone
Avoid medications that can induce hypoglycemia or interfere with fatty acid metabolism
Ensure adequate hydration
Consider treatment for any precipitating illness (e.g., antibiotics for suspected infection).
Supportive Care:
Close monitoring of vital signs, neurological status, and metabolic parameters (blood glucose, electrolytes, ammonia, liver function tests)
Continuous cardiac monitoring may be indicated if arrhythmias are suspected
Manage seizures with appropriate anticonvulsants
Aggressive management of any coexisting infections or complications
Discontinue or minimize fat intake until recovery
Monitor for rhabdomyolysis or cardiac dysfunction if suspected.
Prevention And Long Term Management
Long Term Dietary Management:
Lifelong adherence to a low-fat diet with adequate carbohydrate intake is essential
Avoid prolonged fasting
Educate parents on fasting guidelines: never let affected children fast for more than 8-10 hours without carbohydrate intake
Implement a "sick day rule" that involves increasing carbohydrate intake and avoiding fatty foods during illness.
Carnitine Supplementation:
Routine L-carnitine supplementation is often recommended for MCADD patients to help excrete toxic metabolites and potentially improve energy metabolism
Dosage typically ranges from 50-100 mg/kg/day, divided into two or three doses.
Emergency Preparedness:
Parents and caregivers must be educated about the signs and symptoms of an impending crisis and the immediate steps to take
A detailed emergency plan, including contact information for the metabolic team, should be readily available
Medical alert bracelets or necklaces are recommended.
Monitoring:
Regular follow-up with a metabolic specialist is crucial
Periodic assessment of growth, development, biochemical markers (acylcarnitine profile), and adherence to dietary recommendations
Genetic counseling for affected families.
Complications
Acute Complications:
Hypoglycemia leading to seizures, coma, permanent brain damage
Liver dysfunction and failure
Cardiomyopathy
Rhabdomyolysis
Respiratory distress
Sudden death.
Long Term Sequelae:
Developmental delay
Intellectual disability
Neurological deficits
Motor impairments
Recurrent metabolic crises despite management
Behavioral issues.
Prevention Strategies:
Strict adherence to dietary guidelines and fasting avoidance
Prompt recognition and treatment of illness
Consistent L-carnitine supplementation
Comprehensive parental education and adherence to the emergency plan.
Key Points
Exam Focus:
MCADD is an autosomal recessive disorder of fatty acid oxidation
Presents with hypoketotic hypoglycemia during fasting or illness
Key biochemical findings: elevated C8, C10, C12 acylcarnitines
Emergency management: immediate IV glucose to correct hypoglycemia and prevent catabolism
Long-term: low-fat diet, avoid fasting, L-carnitine supplementation.
Clinical Pearls:
Always consider MCADD in a child with unexplained lethargy, vomiting, and hypoglycemia, especially in the context of an illness
The absence of ketones in hypoglycemia is a critical clue
Early recognition and aggressive glucose administration can prevent devastating neurological sequelae
Educate families about the "sick day rule".
Common Mistakes:
Delaying glucose administration in suspected metabolic crisis
Mistaking hypoketotic hypoglycemia for other causes of hypoglycemia
Inadequate caloric intake during acute illness
Failure to educate parents about long-term management and emergency preparedness
Over-reliance on L-carnitine without addressing glucose provision.