Multiple acyl-CoA deficiency

Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), also known as Glutaric Aciduria Type II, is a rare metabolic disorder characterized by the body's inability to break down certain fats and proteins. This condition is part of a group of disorders known as fatty acid oxidation disorders. MADD is caused by mutations in genes that encode for enzymes called acyl-CoA dehydrogenases, which are crucial for the metabolism of fatty acids and amino acids.

Causes and Genetics

MADD is caused by mutations in several genes, including the ETFA, ETFB, and ETFDH genes. These genes provide instructions for making enzymes that are essential for the proper function of the mitochondrial electron transport chain, which plays a critical role in energy production. Mutations in these genes disrupt the function of the electron transport chain, leading to the accumulation of fatty acids and amino acids in the body.

Classification

MADD is classified into three types based on the onset and severity of symptoms:

• Type I (Neonatal-Onset with Congenital Anomalies)
• Type II (Neonatal-Onset without Congenital Anomalies)
• Type III (Late-Onset)

Symptoms

Symptoms of MADD vary widely among affected individuals and can range from mild to severe. Common symptoms include:

• Hypoglycemia (low blood sugar)
• Metabolic acidosis (increased acidity in the blood)
• Muscle weakness
• Hypotonia (reduced muscle tone)
• Hepatomegaly (enlarged liver)
• Cardiomyopathy (heart muscle disease)
• Respiratory distress
• Failure to thrive in infants

Diagnosis

Diagnosis of MADD involves a combination of clinical evaluation, biochemical tests, and genetic testing. Biochemical tests may show elevated levels of certain organic acids in the urine and abnormal acylcarnitine profile in the blood. Genetic testing can confirm the diagnosis by identifying mutations in the ETFA, ETFB, or ETFDH genes.

Treatment

There is no cure for MADD, but treatment focuses on managing symptoms and preventing metabolic crises. Treatment strategies may include:

• Dietary management to restrict intake of fats and proteins
• Carnitine supplementation to enhance fatty acid oxidation
• Riboflavin (vitamin B2) supplementation, as some forms of MADD respond to riboflavin
• Avoidance of fasting to prevent hypoglycemia

Prognosis

The prognosis for individuals with MADD varies depending on the type and severity of the condition. Early diagnosis and appropriate management can improve the quality of life and reduce the risk of severe complications.

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