Carnitine Palmitoyltransferase II (CPT2) deficiency is an inherited metabolic disorder that affects the body’s ability to process certain fats for energy. This condition specifically hinders the breakdown of long-chain fatty acids, which are a major source of energy for the body, especially during periods without food or during extended physical activity. The disruption in this energy production pathway leads to a range of health issues. This disorder is considered rare and presents with varying degrees of severity.
Genetic Basis of CPT2 Deficiency
CPT2 deficiency is caused by mutations in the CPT2 gene, which holds the instructions for creating the enzyme carnitine palmitoyltransferase II. The CPT2 enzyme operates within the mitochondria, the energy-producing centers of cells. Its job is to transport long-chain fatty acids into the mitochondria to be converted into energy.
When the CPT2 gene has a mutation, the resulting enzyme is either faulty or produced in insufficient amounts. This defect prevents the proper processing of long-chain fatty acids. These fats can then accumulate in tissues like the heart, liver, and muscles, causing damage while depriving the body of an energy supply.
The condition is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated CPT2 gene, one from each parent. People who inherit only one mutated copy are considered carriers. They typically do not show symptoms but can pass the gene to their children.
Forms and Associated Symptoms
The clinical presentation of CPT2 deficiency is categorized into three forms that differ in severity and age of onset. These forms are the myopathic, severe infantile, and lethal neonatal. The specific symptoms and health complications are directly related to which form an individual has.
Myopathic Form
The myopathic form is the most common and mildest version, with symptoms first appearing in childhood or adolescence. It is characterized by recurrent episodes of muscle pain (myalgia) and the breakdown of muscle tissue (rhabdomyolysis). This muscle breakdown releases a protein called myoglobin into the bloodstream, which can cause the urine to become red or brown. These episodes are frequently triggered by factors like prolonged exercise, fasting, or illness. Between attacks, individuals often experience no symptoms.
Severe Infantile Form
The severe infantile form of CPT2 deficiency manifests within the first year of life with serious health problems affecting multiple organ systems. Infants with this form experience episodes of low blood sugar and low ketone levels (hypoketotic hypoglycemia), particularly during illness or fasting. These metabolic crises can lead to an enlarged liver, a weakened heart muscle (cardiomyopathy), irregular heartbeats, and seizures. Without prompt medical intervention, these episodes risk liver failure, lasting nervous system damage, or sudden death.
Lethal Neonatal Form
The lethal neonatal form is the rarest and most severe presentation, with symptoms appearing within the first few days after birth. Newborns with this form experience rapid, multisystem organ failure. They often have severe respiratory distress, liver failure, cardiomyopathy, and life-threatening arrhythmias. Structural abnormalities of the brain and kidneys are also common. Infants with this form of the disorder typically survive for only a few days to a few months.
The Diagnosis Process
The identification of CPT2 deficiency often begins with newborn screening programs. A routine blood spot test, analyzed using tandem mass spectrometry, can detect abnormal levels of compounds called acylcarnitines. Elevated levels of long-chain acylcarnitines in the blood are a strong indicator of a fatty acid oxidation disorder and prompt immediate follow-up.
When symptoms are present in older children or adults with the myopathic form, diagnosis involves targeted tests. Blood and urine tests during a symptomatic episode can reveal elevated levels of muscle enzymes, like creatine kinase, and myoglobin in the urine, confirming rhabdomyolysis. An enzyme assay can also be performed, which directly measures CPT2 enzyme activity in cultured skin cells or a muscle tissue sample.
Molecular genetic testing is a definitive diagnostic method. This analysis of the CPT2 gene identifies the specific disease-causing mutations. Identifying the mutations confirms the diagnosis and can also be used for prenatal testing in future pregnancies if desired by the family.
Management and Lifestyle Adjustments
There is no cure for CPT2 deficiency, so management focuses on preventing symptomatic episodes and responding quickly when they occur. The approach depends on the disorder’s form, but dietary and lifestyle adjustments are central to all management plans. These strategies are particularly effective for individuals with the myopathic form.
Dietary Management
The primary strategy for managing CPT2 deficiency is a specialized diet that is low in fat and high in carbohydrates. The goal is to minimize the intake of long-chain fatty acids and instead provide energy through carbohydrates. An important component of this diet is the use of medium-chain triglyceride (MCT) oil. MCTs are a type of fat that can enter the mitochondria for energy production without needing the CPT2 enzyme, providing an alternative fuel source.
Trigger Avoidance
Managing the condition involves avoiding known triggers that can provoke an episode of muscle breakdown or a metabolic crisis. Patients are advised to prevent prolonged periods of fasting by eating frequent meals and snacks. Strenuous or extended exercise must be avoided, as it places high energy demands on the muscles. Other triggers include infections like the flu, exposure to extreme cold, and emotional stress.
Emergency Care
During an acute episode of rhabdomyolysis, prompt medical treatment is necessary to prevent kidney damage from the high levels of myoglobin. This often involves hospitalization for intravenous (IV) fluids to help flush the kidneys and IV glucose to provide a ready source of energy. For the more severe infantile form, immediate medical care during an illness is needed to manage low blood sugar and prevent severe complications.