VLCAD Deficiency

Our project will focus on a disorder of β-fatty acid oxidation. This disorder is known as Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) deficiency. 

Introduction to VLCADD

VLCAD deficiency is an autosomal recessive disorder. This happens when the enzyme, very long-chain acyl-CoA dehydrogenase, essential to oxidize fatty acids are absent or simply mutated. These results in the inability of the body to oxidize fats from the food we eat or the fatty acids stored in our liver and muscles. In short, the VLCAD deficiency inhibits the oxidation of fats to produce energy. 

 
VLCAD is an enzyme that is encoded by the acyl-CoA dehydrogenase very long chain gene (ACADVL). The ACADVL gene is 5.4 kb long containing 20 exons and is found on chromosome 17 between bands p11.2 and p11.13105. However, the ACADVL is infamously known to have “more than 100 mutations” that causes VLCAD deficiency. Mutations in the ACADVL gene will lead to a truncated VLCAD enzyme. An example is a deletion mutation that causes the VLCAD to be a truncated protein. Since the VLCAD is shorter than it should be, it won’t be able to carry out its normal function. Therefore, fatty acid oxidation cannot be carried out properly. 
 
When a person is said to be suffering from VLCAD deficiency, they will feel lethargy and incur low blood sugar-hypoglycemia- as our body relies on a limited amount of glucose for energy. Furthermore, death may consume a patient because all the unconverted fats will accumulate in tissues and damage the liver, heart and muscles.





Biochemistry behind VLCADD

Normal fatty acid oxidation can go from carbon-16 or carbon-18 down to carbon-4 and carbon-4 will produce “ketone bodies” in the liver that can be exported to other organs as a source of acetyl-CoA for energy production from their citric acid cycle. 

In VLCAD deficiency the ability to produce and export these “ketone bodies” is severely diminished thus causing energy deficits in other organs that depend on them for energy production. This is especially true for skeletal muscle and the heart and results in muscle cell breakdown  and cardiomyopathy with heart failure during illness in the severe form of VLCADD.

References:

Unknown. (n.d.) ACADVL Gene in genomic location. [image online] Available at: http://www.genecards.org/cgi-bin/carddisp.pl?gene=ACADVL [Accessed: 16th January 2013].  
 
R.Roe, C. (2011) My experiences and understanding of VLCAD deficiency and its treatment. [e-book] p.1. http://www.fodsupport.org/documents/DrRoeandVLCADexperiencesEdited2011.pdf [Accessed: 5th January 2013].

Unknown. (2010) rip-tombstone. [image online] Available at: http://www.forevergeek.com/2010/03/death_and_the_web_inevitable_tech_decisions/rip-tombstone/ [Accessed: 10th January 2013]. 

Unknown. (2005) Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD). [image online] Available at: http://www.ct.gov/dph/lib/dph/family_health/newborn_screening/pdf/hpvlcadd.pdf [Accessed: 1st January 2013].