Acyl-CoA dehydrogenase, medium chain, deficiency of

A genetic disorder affecting fatty acid metabolism

Medium-chain acyl-CoA dehydrogenase deficiency
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Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Hypoglycemia, lethargy, seizures
Complications	N/A
Onset	Infancy or early childhood
Duration	Lifelong
Types	N/A
Causes	Mutations in the ACADM gene
Risks	N/A
Diagnosis	Newborn screening, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Dietary management, avoidance of fasting
Medication	N/A
Prognosis	Good with treatment
Frequency	N/A
Deaths	N/A

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an inborn error of metabolism that affects the body's ability to break down medium-chain fatty acids into energy. This condition is caused by mutations in the ACADM gene, which encodes the enzyme medium-chain acyl-CoA dehydrogenase (MCAD). This enzyme is crucial for the beta-oxidation of fatty acids in the mitochondria, a process that provides energy during periods of fasting.

Pathophysiology

MCAD is an enzyme that catalyzes the initial step in the mitochondrial beta-oxidation of medium-chain fatty acids. In individuals with MCADD, the deficiency of this enzyme leads to an accumulation of medium-chain fatty acids and their derivatives, which can be toxic. This accumulation can result in hypoglycemia, hypoketotic hypoglycemia, and metabolic crisis, especially during periods of fasting or illness when the body relies on fat stores for energy.

Genetics

MCADD is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated ACADM gene, one from each parent. The most common mutation associated with MCADD is the c.985A>G (K304E) mutation, although other mutations have been identified.

Clinical Presentation

Symptoms of MCADD typically present in infancy or early childhood and may include:

• Lethargy
• Vomiting
• Seizures
• Hypoglycemia
• Coma

If untreated, MCADD can lead to serious complications such as sudden infant death syndrome (SIDS) or Reye-like syndrome.

Diagnosis

MCADD is often detected through newborn screening programs, which test for elevated levels of medium-chain acylcarnitines in the blood. Confirmatory diagnosis is made through genetic testing to identify mutations in the ACADM gene.

Management

The primary treatment for MCADD involves dietary management to prevent fasting and ensure adequate caloric intake. This includes:

• Frequent feeding, especially in infants and young children
• A diet high in carbohydrates and low in fats
• Supplementation with carnitine in some cases

During illness or periods of increased metabolic stress, intravenous glucose may be necessary to prevent hypoglycemia.

Prognosis

With early diagnosis and proper management, individuals with MCADD can lead normal, healthy lives. However, it is crucial to avoid fasting and to manage metabolic stress promptly to prevent complications.

Also see

• Fatty acid metabolism disorders
• Carnitine palmitoyltransferase I deficiency
• Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
• Newborn screening