Carnitine palmitoyltransferase II deficiency
Carnitine palmitoyltransferase II (CPT II) deficiency blocks the use of certain fats for energy, especially during fasting, and presents in three severity‑graded forms.
Overview
Carnitine palmitoyltransferase II deficiency is a genetic disorder that prevents the body from using specific fats for energy, particularly during periods of fasting. The condition is classified into three main types that differ in severity and age of onset: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.
Symptoms
Lethal neonatal form
- Respiratory failure
- Liver failure
- Cardiomyopathy (weak heart muscle)
- Arrhythmia (irregular heartbeat)
- Structural abnormalities of the brain and kidneys (in many cases)
- Hypoketotic hypoglycemia (low blood glucose with low ketones)
- Seizures or coma after prolonged fasting
Infants with this form usually survive only a few days to a few months.
Severe infantile hepatocardiomuscular form
- Recurring hypoketotic hypoglycemia
- Seizures
- Liver dysfunction
- Cardiomyopathy and arrhythmia
- Myopathy (muscle weakness in arms and legs)
- Triggers: fasting or viral infections
- Risks: liver failure, nervous system damage, coma, sudden death
Myopathic form (least severe)
- Recurrent muscle pain (myalgia)
- Occasional muscle weakness associated with rhabdomyolysis
- Myoglobinuria (red or brown urine due to excess myoglobin)
- Triggers: exercise, stress, extreme temperatures, infections, fasting
- First episode typically in childhood or adolescence
- Variable severity and frequency; asymptomatic between episodes
Causes & Risk Factors
Pathogenic CPT2 gene variants cause CPT II deficiency. The CPT2 gene encodes the enzyme carnitine palmitoyltransferase 2, which is essential for fatty acid oxidation within mitochondria. Variants reduce enzyme activity, preventing removal of carnitine from long‑chain fatty acids. Consequently, long‑chain acylcarnitines accumulate, leading to the clinical features described above.
This condition is inherited in an autosomal recessive manner: both copies of the gene must carry pathogenic variants for disease manifestation. Parents are typically carriers without symptoms, though rare carriers may experience myopathic symptoms after strenuous activity.
Diagnosis
- Newborn screening that detects elevated blood levels of long‑chain acylcarnitines.
- Clinical evaluation of characteristic symptoms (e.g., hypoketotic hypoglycemia, myalgia, cardiomyopathy).
- Genetic testing to identify pathogenic variants in the CPT2 gene.
Treatment & Management
- Avoid long periods of fasting.
- Limit intensive or prolonged exercise that may trigger rhabdomyolysis.
- Prompt treatment of infections and other metabolic stressors.
- Supportive care during acute episodes (e.g., glucose infusion to prevent hypoglycemia).
- Genetic counseling for families.
Other Names
- Carnitine palmitoyltransferase 2 deficiency
- CPT II deficiency
- CPT2 deficiency
Frequency
CPT II deficiency is rare. The lethal neonatal form has been reported in at least 20 families, the severe infantile hepatocardiomuscular form in approximately 30 families, and the myopathic form in more than 300 reported cases.