Carnitine palmitoyl transferase II deficiency, severe infantile form

Carnitine palmitoyl transferase II (CPT II) deficiency, severe infantile form, is a rare and life-threatening inherited disorder of long-chain fatty acid oxidation. It is caused by mutations in the CPT2 gene, which encodes the enzyme carnitine palmitoyltransferase II, located on the inner mitochondrial membrane. This enzyme is essential for transporting long-chain fatty acids into the mitochondria for beta-oxidation and energy production. In the severe infantile form, enzyme activity is profoundly reduced, leading to an inability to utilize long-chain fatty acids as fuel, particularly during periods of fasting or metabolic stress. This form is distinct from the milder, more common adult muscular form and the lethal neonatal form of CPT II deficiency. The severe infantile form typically presents within the first year of life, often between 6 and 24 months of age, with hypoketotic hypoglycemia, liver failure, cardiomyopathy, and seizures. Affected infants may experience episodes of metabolic crisis triggered by fasting, illness, or fever. The liver, heart, and skeletal muscles are the primary organ systems affected. Hepatomegaly is common, and liver dysfunction can be severe. Cardiac involvement includes dilated or hypertrophic cardiomyopathy, which can lead to arrhythmias and cardiac failure. Skeletal muscle weakness and elevated creatine kinase levels may also be observed. Some patients may have renal tubular abnormalities. Treatment is primarily supportive and preventive. Management focuses on avoiding prolonged fasting, providing a diet low in long-chain fats and supplemented with medium-chain triglycerides (MCT), which bypass the CPT II enzyme for mitochondrial entry. During acute metabolic crises, intravenous glucose administration is critical to prevent hypoglycemia and suppress fatty acid mobilization. Carnitine supplementation may be considered, though its use remains debated. Despite treatment, the prognosis for the severe infantile form is guarded, with significant morbidity and mortality, particularly from cardiac complications and recurrent metabolic decompensation. Early diagnosis through newborn screening programs using tandem mass spectrometry and prompt dietary management may improve outcomes.

Common questions about Carnitine palmitoyl transferase II deficiency, severe infantile form