Carnitine Palmitoyltransferase II (CPT II) deficiency is a rare genetic metabolic disorder affecting the body’s ability to process fats. It hinders the conversion of long-chain fatty acids into usable energy, especially when the body relies on fat stores, like during fasting or increased energy demands. This disruption affects a fundamental energy-producing pathway.
Understanding Carnitine Palmitoyltransferase II Deficiency
The CPT II enzyme is located within the mitochondria of cells, playing a role in energy production. Mitochondria, often called the “powerhouses” of the cell, generate most cellular energy. CPT II facilitates the transport of long-chain fatty acids from the cytoplasm into the mitochondrial matrix. Inside the mitochondria, these fatty acids undergo beta-oxidation, breaking them down to produce adenosine triphosphate (ATP), the cell’s primary energy currency.
When the CPT II enzyme is deficient, long-chain fatty acids cannot efficiently enter the mitochondria for energy. This impaired transport deprives cells of a significant energy source, especially during high energy needs, and causes unutilized fatty acids to accumulate outside the mitochondria. The buildup of these fatty acids and their derivatives can become toxic, contributing to the symptoms of CPT II deficiency. Tissues heavily reliant on fat for energy, such as muscles and the heart, are particularly vulnerable to dysfunction.
Recognizing the Signs
CPT II deficiency presents in three primary forms, varying by symptom onset and severity. The most common is the myopathic form, manifesting in adolescence or adulthood. Individuals experience recurrent episodes of muscle pain, weakness, and stiffness, especially after prolonged exercise, fasting, or cold exposure. These episodes can lead to rhabdomyolysis, where muscle fibers break down and release contents into the bloodstream, sometimes causing dark urine due to myoglobinuria.
The severe infantile form appears during early infancy. It can involve liver dysfunction, characterized by an enlarged liver and elevated enzymes. Cardiomyopathy (heart muscle disease) and recurrent hypoglycemia (low blood sugar) are also common. Neurological symptoms like seizures can occur, reflecting the systemic metabolic disturbance.
The lethal neonatal form is evident shortly after birth. It is characterized by profound multi-organ failure, affecting the liver, heart, and kidneys. Infants may also exhibit brain abnormalities and distinctive facial features. This severe derangement often leads to a poor prognosis, with affected infants typically succumbing within days or weeks.
Diagnosis and Genetic Basis
Diagnosis of CPT II deficiency involves laboratory tests and genetic analysis. Newborn screening programs can identify the condition early by detecting elevated specific acylcarnitines in blood spots. For older individuals, blood tests, particularly an acylcarnitine profile, can reveal characteristic patterns of fatty acid metabolites suggesting CPT II deficiency. These profiles show increased long-chain acylcarnitines.
Further confirmation involves measuring CPT II enzyme activity in cultured skin fibroblasts or muscle tissue. Reduced enzyme activity indicates the disorder. The definitive diagnosis relies on genetic testing, which identifies specific mutations in the CPT2 gene. This gene provides instructions for making the CPT II enzyme, and mutations disrupt its function.
CPT II deficiency is inherited in an autosomal recessive pattern. An individual must inherit two copies of the mutated CPT2 gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene are typically unaffected and are referred to as carriers. Each child of two carrier parents has a 25% chance of inheriting two mutated copies and developing the condition, a 50% chance of being a carrier, and a 25% chance of inheriting two normal copies.
Managing the Condition
Managing CPT II deficiency primarily focuses on preventing symptoms and metabolic crises through dietary modifications and lifestyle adjustments. A low-fat, high-carbohydrate diet is generally recommended to reduce the body’s reliance on fatty acid oxidation for energy. Individuals are advised to consume frequent meals and snacks to avoid prolonged fasting, which can deplete glycogen stores and trigger symptoms. In some cases, supplementation with medium-chain triglycerides (MCT oil) can provide an alternative energy source, as MCTs do not require the CPT II enzyme for transport into the mitochondria.
Avoiding known triggers is a cornerstone of management. This includes preventing prolonged or intense physical exercise, as well as exposure to cold temperatures, all of which increase energy demands. Certain medications that interfere with fatty acid metabolism may also need to be avoided. During periods of illness, such as infections, there is an increased risk of metabolic decompensation.
Immediate medical attention is necessary during illnesses or if symptoms of a metabolic crisis appear. Administering intravenous glucose is a common intervention to provide an immediate energy source and prevent muscle breakdown or other severe complications. Ongoing monitoring by a multidisciplinary medical team, including metabolic specialists, nutritionists, and other relevant specialists, is important to adjust management strategies and address any emerging health concerns.
References
https://www.ncbi.nlm.nih.gov/books/NBK1135/ https://www.nbi.nlm.nih.gov/books/NBK151049/