Medium-chain acyl-coenzyme A dehydrogenase deficiency

Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD)
Synonyms	Carnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency, MCAD deficiency, MCADD
Pronounce
Field	Endocrinology, Genetics, Pediatrics
Symptoms	Hypoglycemia, lethargy, vomiting, seizures
Complications	Encephalopathy, metabolic crisis, coma, sudden death
Onset	Infancy or early childhood
Duration	Lifelong
Types
Causes	Genetic mutation in ACADM gene
Risks	Family history, autosomal recessive inheritance
Diagnosis	Newborn screening, biochemical testing, genetic testing
Differential diagnosis	Other fatty acid oxidation disorders, glycogen storage diseases
Prevention	Dietary management, avoidance of fasting, regular monitoring
Treatment	Dietary adjustments, glucose supplementation during illness
Medication	Carnitine supplementation
Prognosis	Generally good with early diagnosis and proper management
Frequency	Approximately 1 in 10,000 to 15,000 births
Deaths	Rare, primarily if untreated or during metabolic crises

MCAD is one of the enzymes responsible for dehydrogenation of fatty acids as they cycle through the beta-oxidation spiral.

Acylcarnitine profile of an individual with MCADD, showing characteristic elevation of octanoylcarnitine (C8).

Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD), also known as MCAD deficiency or MCADD, is an inherited autosomal recessive metabolic disorder. It results from mutations in the ACADM gene, affecting the body's ability to break down medium-chain fatty acids into energy.

Signs and Symptoms

Symptoms typically present in infancy or early childhood and include:

• Hypoglycemia (low blood sugar)
• Lethargy and fatigue
• Vomiting
• Seizures
• Episodes of metabolic crisis triggered by fasting or illness

Causes

MCAD deficiency is caused by mutations in the ACADM gene. These mutations lead to reduced activity or absence of the enzyme medium-chain acyl-coenzyme A dehydrogenase, essential for fatty acid oxidation.

Risk Factors

Risk factors include:

• Family history of MCAD deficiency
• Autosomal recessive genetic inheritance pattern

Diagnosis

MCAD deficiency is typically diagnosed via:

• Newborn screening programs
• Biochemical tests showing elevated medium-chain fatty acids
• Genetic testing confirming mutations in the ACADM gene

Differential Diagnosis

Conditions with similar clinical presentations include:

• Other fatty acid oxidation disorders
• Glycogen storage diseases

Treatment and Management

Effective management strategies include:

• Avoiding prolonged fasting
• Dietary modifications with frequent feeding
• Glucose supplementation during illness or stress
• Carnitine supplementation to support metabolic pathways

Prognosis

With timely diagnosis and appropriate management, individuals with MCAD deficiency typically have a good prognosis. However, untreated or mismanaged cases may result in severe complications, including metabolic crises and sudden death.

Epidemiology

MCAD deficiency occurs in approximately 1 in 10,000 to 15,000 live births, making it one of the most common fatty acid oxidation disorders.

Prevention

Preventive measures include early diagnosis through newborn screening, regular dietary monitoring, and patient education regarding illness management to prevent metabolic crises.

External links

• CDC MCADD
• NIH MCADD