Which are the causes of Very Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD)?

Very Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD) is a rare genetic disorder that affects the body's ability to break down certain fats for energy. It is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene, one from each parent, in order to develop the condition. LCAD deficiency is caused by mutations in the ACADVL gene, which provides instructions for producing an enzyme called very long chain acyl-CoA dehydrogenase.

The ACADVL gene mutations result in a deficiency or complete absence of the enzyme, leading to the accumulation of very long chain fatty acids in various tissues and organs. These fatty acids cannot be properly metabolized and utilized for energy production, causing a range of symptoms and complications.

The exact causes of ACADVL gene mutations are not fully understood, but they are believed to be primarily genetic in nature. Some individuals may inherit the defective gene from both parents, while others may have a spontaneous mutation in the gene. Certain populations, such as the Old Order Amish community, have a higher prevalence of LCAD deficiency due to a specific mutation that is more common in these groups.

LCAD deficiency can present in different ways depending on the severity of the enzyme deficiency. In some cases, affected individuals may experience symptoms in infancy or early childhood, while others may not develop symptoms until later in life. The severity of the condition can also vary widely, ranging from mild to life-threatening.

Common symptoms of LCAD deficiency include:

• Poor feeding and failure to thrive in infancy


• Low blood sugar (hypoglycemia)


• Muscle weakness and fatigue


• Enlarged liver (hepatomegaly)


• Heart abnormalities


• Developmental delays


• Seizures

Diagnosis of LCAD deficiency involves a combination of clinical evaluation, biochemical testing, and genetic testing. Blood tests can reveal elevated levels of certain fatty acids and specific metabolites, while genetic testing can confirm the presence of ACADVL gene mutations.

Management of LCAD deficiency primarily involves dietary interventions and close monitoring. Individuals with LCAD deficiency may require a low-fat, high-carbohydrate diet to provide alternative sources of energy. They may also need to avoid fasting and maintain regular meal schedules to prevent hypoglycemia. Additionally, certain supplements and medications may be prescribed to help manage symptoms and prevent complications.

In conclusion, Very Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD) is a rare genetic disorder caused by mutations in the ACADVL gene. The exact causes of these gene mutations are not fully understood, but they are believed to be primarily genetic in nature. LCAD deficiency can present with a range of symptoms and severity levels, and diagnosis involves a combination of clinical evaluation, biochemical testing, and genetic testing. Management of the condition primarily involves dietary interventions and close monitoring to prevent complications.