carnitine palmitoyl transferase II deficiency, severe infantile form

Carnitine palmitoyl transferase II deficiency, severe infantile form, is a metabolic condition that disrupts the body’s ability to break down long-chain fatty acids inside mitochondria, the energy-producing parts of the cell. Symptoms begin in early infancy and involve the heart, liver, skeletal muscles, and metabolic balance. The condition results from pathogenic variants in the CPT2 gene, which provides instructions for the CPT II enzyme critical to fatty-acid oxidation. It affects males and females equally and is considered very rare, occurring in fewer than one in one million people worldwide. Severity and symptoms vary widely between individuals, even among siblings diagnosed in the same family.

Infants with this disorder often come to medical attention because of sudden metabolic crises marked by hypoketotic hypoglycemia, respiratory arrest, or life-threatening heart rhythm disturbances such as ventricular tachycardia. Cardiovascular involvement is striking, and cardiomegaly with weakened heart muscle function can be present very early. Metabolic decompensation episodes are frequently accompanied by dramatic elevations of blood lactate dehydrogenase and creatine kinase. Muscle-related features include painful muscle cramps, exercise intolerance, myalgia, and intermittent weakness. In some episodes, muscle breakdown (rhabdomyolysis) leads to red-brown urine due to myoglobinuria. Between crises, many children appear well, but cold exposure, fasting, or illness can trigger sudden deterioration. The liver can enlarge (hepatomegaly), and blood tests may show elevated transaminases. Reduced CPT II enzyme activity and characteristic increases in long-chain acylcarnitines in blood are common laboratory findings. Not all individuals experience every feature, and the intensity of episodes can range from mild weakness to severe, sudden decompensation.

Carnitine palmitoyl transferase II deficiency is caused by alterations in the CPT2 gene, which encodes the CPT II enzyme responsible for transporting long-chain fatty acids into mitochondria for energy production. When the enzyme does not function properly, cells cannot use these fats for fuel, leading to energy shortages and toxic metabolite accumulation, particularly during fasting or illness. The disorder is inherited in an autosomal recessive pattern. This means a child must receive one non-working copy of CPT2 from each parent to be affected. Parents who each carry a single altered copy are typically healthy carriers but have a 25 percent chance with every pregnancy of having an affected child. The condition is more common when parents share a common ancestor, because relatives are more likely to carry the same rare genetic variant. Carrier testing and genetic counseling can clarify risks for relatives and support family planning.

Currently, management focuses on supportive care and preventing metabolic crises. Families work closely with metabolic and cardiology specialists to develop an emergency plan that includes rapid treatment of low blood sugar, avoidance of prolonged fasting, and careful monitoring during illnesses. A high-carbohydrate diet with regular meals and bedtime cornstarch supplementation may help some children maintain energy stores, while long-chain fatty acid restriction and substitution with medium-chain triglycerides can reduce toxin buildup. Long-term management includes regular surveillance for potential complications. Cardiac evaluations, including echocardiography and rhythm monitoring, help detect emerging heart problems. Liver function tests and creatine kinase levels are checked periodically to gauge metabolic stability. Physical and occupational therapy support motor development after episodes of muscle weakness. Because care often involves cardiologists, metabolic specialists, dietitians, and genetic counselors, a multidisciplinary team approach is essential. Patients should discuss individual treatment strategies, emergency protocols, and surveillance schedules with their healthcare team.

The severe infantile form can be life-threatening, especially during early childhood when metabolic demands are high. Some infants experience sudden cardiac events or respiratory arrest during their first crisis, while others achieve better stability with early diagnosis, careful dietary management, and prompt treatment of intercurrent illnesses. Outcomes described in medical literature continue to evolve as standards of care improve. Access to specialized metabolic centers and vigilant monitoring has allowed many affected children to survive longer and experience better quality of life than historical reports suggested. Because the course is highly variable, long-term outlook depends on factors such as the frequency and severity of metabolic crises, cardiac involvement, and how quickly treatment is initiated during illness. Families often find it helpful to connect with metabolic specialists and patient support networks, and genetic counseling can guide family planning and carrier testing for relatives.