CPT2 deficiency is caused by mutations in the CPT2 gene, which encodes the enzyme carnitine palmitoyltransferase II. This enzyme plays a critical role in the process of breaking down long-chain fatty acids into energy within the mitochondria, the energy-producing structures inside cells. When CPT2 is deficient or dysfunctional, the body cannot effectively convert certain fats into usable energy, especially during times when glucose (sugar) is scarce, such as fasting or prolonged exercise.
The CPT2 gene mutations are inherited in an autosomal recessive pattern, meaning a person must inherit two defective copies of the gene—one from each parent—to develop the condition. If only one defective gene is inherited, the person is typically a carrier without symptoms. The mutations lead to a reduction or loss of CPT2 enzyme activity, impairing the transport and metabolism of long-chain fatty acids.
Because fatty acids are a major energy source for muscles and other tissues during periods without food intake, CPT2 deficiency primarily affects energy production in muscle cells and other organs. This results in symptoms such as muscle weakness, exercise intolerance, muscle breakdown (myoglobinuria), low blood sugar, seizures, liver problems, and heart issues like cardiomyopathy.
There are three recognized forms of CPT2 deficiency, differing in age of onset and severity:
1. **Adult (myopathic) form:** The most common form, usually presenting in adolescence or adulthood, characterized mainly by muscle symptoms triggered by prolonged exercise, fasting, or illness.
2. **Infantile form:** Appears in infancy or early childhood, with more severe symptoms including liver failure, hypoglycemia (low blood sugar), seizures, and heart problems.
3. **Neonatal form:** The most severe, presenting at or shortly after birth with life-threatening symptoms including multi-organ failure.
The underlying cause in all forms is the inability of mitochondria to properly metabolize long-chain fatty acids due to defective CPT2 enzyme function. This disrupts the normal energy supply, especially when the body relies on fat metabolism during fasting or stress.
In summary, CPT2 deficiency arises from inherited mutations in the CPT2 gene that impair the enzyme’s role in mitochondrial fatty acid oxidation, leading to energy production failure and a spectrum of clinical symptoms depending on the severity and timing of enzyme dysfunction.
