Medium-chain Acyl-CoA dehydrogenase deficiency

Medium-chain Acyl-CoA Dehydrogenase Deficiency

Medium-chain Acyl-CoA Dehydrogenase Deficiency (MCADD) is a genetic disorder that affects the body's ability to convert certain fats to energy, particularly during periods without food (fasting). It is one of the most common fatty acid oxidation disorders and is inherited in an autosomal recessive pattern.

Pathophysiology

MCADD is caused by mutations in the ACADM gene, which provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase. This enzyme is essential for the breakdown of medium-chain fatty acids, a process that occurs in the mitochondria of cells. When this enzyme is deficient or absent, medium-chain fatty acids cannot be effectively broken down, leading to an accumulation of fatty acids and a deficiency of ketones, which are crucial energy sources during fasting.

Symptoms

Symptoms of MCADD typically appear in infancy or early childhood and can include:

• Hypoglycemia (low blood sugar)
• Lethargy
• Vomiting
• Seizures
• Coma

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

Diagnosis

MCADD is often diagnosed through newborn screening programs, which test for elevated levels of certain acylcarnitines in the blood. Confirmatory testing involves genetic testing to identify mutations in the ACADM gene.

Treatment

Management of MCADD involves preventing fasting and ensuring a regular intake of calories, especially during illness or stress. Dietary management may include:

• Frequent meals and snacks
• A diet high in carbohydrates and low in fats
• Supplementation with carnitine in some cases

Prognosis

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

Genetics

MCADD is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent. Carriers, who have one normal and one mutated gene, typically do not show symptoms.

Epidemiology

MCADD is one of the most common fatty acid oxidation disorders, with an estimated incidence of 1 in 10,000 to 1 in 20,000 live births in the United States.

Also see

• Fatty acid metabolism
• Newborn screening
• Genetic disorders
• Metabolic disorders