Decreased tissue utilization of long-chain fatty acids (LCFA) as a fuel occurs in carnitine deficiencies. Primary carnitine deficiency is characterized by a malfunctioning membrane transporter that hinders the uptake of carnitine by the heart, skeletal muscle, and kidneys, resulting in its excretion. Supplementation with carnitine is the recommended treatment. Secondary carnitine deficiency arises primarily due to defects in fatty acid oxidation, leading to the accumulation of acylcarnitines excreted in urine and reducing the availability of carnitine. Acquired secondary carnitine deficiency can occur in patients with liver disease, where carnitine synthesis is decreased, or in individuals taking valproic acid, an antiseizure drug that impairs renal reabsorption of carnitine. (Note: Mitochondrial oxidation defects can also be caused by deficiencies in CPT-I and CPT-II. CPT-I deficiency severely impairs the liver's ability to synthesize glucose during fasting, leading to severe hypoglycemia, coma, and potential fatality. CPT-II deficiency affects the liver, cardiac muscle, and skeletal muscle. The most common form primarily affects skeletal muscle, resulting in muscle weakness and myoglobinemia after prolonged exercise. Treatment involves avoiding fasting and adopting a high-carbohydrate, low-fat diet supplemented with medium-chain triglycerides.) 

Fatty acids with a chain length of 12 carbons or fewer can enter mitochondria without relying on carnitine or the CPT system. Once inside the mitochondria, these fatty acids are activated to their CoA derivatives by matrix enzymes and undergo oxidation. (Note: Human milk is rich in medium-chain fatty acids, which do not require CPT-I for oxidation and are not inhibited by malonyl CoA.)
Carnitine deficiencies: Such deficiencies result in decreased ability of tissues to use LCFA as a fuel. Primary carnitine deficiency is caused by defects in a membrane transporter that prevent uptake of carnitine by cardiac and skeletal muscle and the kidneys, causing carnitine to be excreted. Treatment includes carnitine supplementation. Secondary carnitine deficiency occurs primarily as a result of defects in fatty acid oxidation leading to the accumulation of acylcarnitines that are excreted in the urine, decreasing carnitine availability. Acquired secondary carnitine deficiency can be seen, for example, in patients with liver disease (decreased carnitine synthesis) or those taking the antiseizure drug valproic acid (decreased renal reabsorption). [Note: Defects in mitochondrial oxidation can also be caused by deficiencies in CPT-I and CPT-II. CPT-I deficiency affects the liver, where an inability to use LCFA for fuel greatly impairs that tissue’s ability to synthesize glucose (an endergonic process) during a fast. This can lead to severe hypoglycemia, coma, and death. CPT-II deficiency can affect the liver and cardiac and skeletal muscle. The most common (and least severe) form affects skeletal muscle. It presents as muscle weakness with myoglobinemia following prolonged exercise. Treatment includes avoidance of fasting and adopting a diet high in carbohydrates and low in fat but supplemented with medium-chain TAG.] 2.
Shorter-chain fatty acid entry into mitochondria: Fatty acids ≤12 carbons can cross the inner mitochondrial membrane without the aid of carnitine or the CPT system. Once inside the mitochondria, they are activated to their CoA derivatives by matrix enzymes and are oxidized. [Note: Medium-chain fatty acids are plentiful in human milk. Because their oxidation is not dependent on CPT-I, malonyl CoA is not inhibitory.] 3.