LC-FAOD are rare, genetic metabolic disorders that prevent the body from breaking down long-chain fatty acids into energy during metabolism.
You may identify with a certain type of LC-FAOD:
CPT I (carnitine palmitoyltransferase I) deficiency
A mutation in the CPTIA gene causes the CPT I enzyme to not function properly, which results in CPT I deficiency. This means that long-chain fatty acids cannot begin the first step in the carnitine shuttle to bring long-chain fatty acids into the mitochondrion. Key signs and symptoms usually appear in childhood and can include neurological problems related to poor liver function and low levels of ketones and sugar in the blood.
CACT (carnitine-acylcarnitine translocase) deficiency
A mutation in the SLC25A20 gene causes CACT deficiency. This means that the middle step of the carnitine shuttle, transporting the long-chain fatty acid into the mitochondrion, cannot be performed properly. Key signs and symptoms can include low levels of ketones and sugar in the blood, respiratory distress, neurological problems, muscle weakness, heart problems, and high levels of ammonia in the blood.
CPT II (carnitine palmitoyltransferase II) deficiency
Mutations in the CPT2 gene cause CPT II deficiency. This means that the last step in the carnitine shuttle cannot be completed. Therefore, long-chain fatty acids cannot enter the mitochondrion. There are two forms of CPT II deficiency. One form appears in newborns and infants and can cause low levels of ketones and sugar in the blood, problems with the heart muscle, and neurological problems. The other form can appear at any age and can cause muscle pain and weakness after exercise.
VLCAD (very long-chain acyl-CoA dehydrogenase) deficiency
A mutation in the ACADVL gene causes VLCAD deficiency. This enzyme is part of the long-chain beta oxidation spiral. Once long-chain fatty acids enter the mitochondria after transportation via the carnitine shuttle, they are processed by the long-chain beta oxidation spiral. If the VLCAD enzyme is not functioning properly, then long-chain fatty acids are not broken down properly, resulting in lower energy and damage from incomplete processing of fatty acids. There are three major forms of VLCAD deficiency. One form appears in early childhood and can cause problems with the heart muscle. A second form appears later in childhood, often with low levels of ketones and sugar in the blood. The third form affects adults and can cause muscle symptoms, usually after exercising.
TFP (trifunctional protein) deficiency
TFP deficiency occurs when a person has a mutation in both the HADHA gene and HADHB gene. TFP is a three enzyme complex and performs the last three steps in the breakdown of long-chain fatty acids. One of these enzymes is LCHAD. If the TFP enzyme complex is not working properly, long-chain fatty acids cannot be broken down for energy and unused fatty acids can build up in the body and cause issues. Key signs and symptoms can include heart disease and muscle weakness.
LCHAD (long-chain 3-hydroxy-acyl-CoA dehydrogenase) deficiency
LCHAD deficiency occurs when a person has a mutation in the HADHA gene. This is part of the TFP complex (see TFP), but the mutation is just in the HADHA gene, causing LCHAD deficiency. If there is a deficiency in this step, long-chain fatty acids are not properly broken down so they cannot be used for energy. Key signs and symptoms can include low levels of ketones and sugar in the blood, liver disease, problems with the heart muscle, muscle weakness, nerve pain in the hands and feet, and an eye condition called pigmentary retinopathy.
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