Demystifying Very Long-Chain Fatty Acid Accumulation: Genetic Testing and Potential Therapies

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Very long-chain fatty acid (VLCFA) accumulation is a condition that occurs when the body is unable to break down certain types of fats. This can lead to a variety of health issues, including neurological disorders and liver diseases. Recent research has shed light on potential therapies and the importance of genetic testing in understanding, diagnosing, and managing this condition. In this article, we will delve into the complexities of VLCFA accumulation, explore the benefits of genetic testing, and discuss promising therapeutic options.

Understanding Very Long-Chain Fatty Acid Accumulation

VLCFAs are essential components of cellular membranes and play critical roles in various biological processes. However, when these fatty acids accumulate in the body, they can cause damage to cells and tissues. VLCFA accumulation is associated with several genetic disorders, such as adrenoleukodystrophy (ALD) and Zellweger syndrome, which can manifest in a wide range of symptoms, including developmental delays, vision loss, and seizures.

Adrenoleukodystrophy and Nervonic Acid Therapy

Adrenoleukodystrophy is a rare genetic disorder characterized by the accumulation of VLCFAs in the brain and adrenal glands. A recent study found that nervonic acid, a monounsaturated fatty acid, can reverse VLCFA accumulation in ALD patient-derived fibroblasts, potentially improving cellular function and offering a therapeutic option (source).

Peroxisomal Multifunctional Protein-2 Deficiency

Another genetic disorder related to VLCFA accumulation is peroxisomal multifunctional protein-2 (MFP2) deficiency. MFP2 deficiency in the adult brain can lead to neuroinflammation and the degeneration of Purkinje cells, which are essential for motor coordination. This degeneration is independent of VLCFA degradation or oligodendrocyte activity (source).

Diagnosing VLCFA Accumulation: The Role of Genetic Testing

Genetic testing is crucial for diagnosing VLCFA accumulation and related disorders. By analyzing a person’s DNA, healthcare professionals can identify mutations in specific genes that may cause the accumulation of VLCFAs. Early diagnosis can help patients and their families make informed decisions about treatment options and manage the condition more effectively.

Benefits of Genetic Testing for VLCFA Accumulation

Genetic testing offers several benefits for individuals with VLCFA accumulation and their families, including:

• Early diagnosis and intervention
• Improved understanding of the condition and its progression
• Identification of carrier status for family planning purposes
• Guidance in choosing appropriate treatment options

Potential Therapies for VLCFA Accumulation

While there is currently no cure for genetic disorders associated with VLCFA accumulation, recent research has identified potential therapeutic options that may help manage symptoms and improve quality of life.

Alleviating Nonalcoholic Fatty Liver Disease

One study found that inhibiting fatty acid translocase (FAT/CD36) palmitoylation can alleviate nonalcoholic fatty liver disease by promoting the localization of FAT/CD36 to hepatocyte mitochondria, enhancing fatty acid oxidation, and reducing lipid accumulation (source).

Camelina Sativa’s Class A LPAT2

Another potential therapy involves the class A lysophosphatidic acid acyltransferase 2 (LPAT2) from Camelina sativa, a plant species. This enzyme promotes VLCFA accumulation in phospholipids and triacylglycerol, providing a promising gene resource for VLCFA production (source).

In conclusion, understanding and diagnosing VLCFA accumulation is vital for managing the condition and improving the quality of life for affected individuals. Genetic testing plays a crucial role in early diagnosis and treatment planning. As research continues to advance, more effective therapies may become available to help those living with VLCFA accumulation and related disorders.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)