Carnitine palmitoyltransferase II deficiency

Acyl-CoA from cytosol to the mitochondrial matrix

Carnitine palmitoyltransferase II deficiency (CPT II deficiency) is a genetic disorder that affects the way the body processes fats. This condition is part of a group of disorders known as fatty acid oxidation disorders, which interfere with the body's ability to convert certain fats into energy. Specifically, CPT II deficiency affects an enzyme called carnitine palmitoyltransferase II, which is essential for the transport of long-chain fatty acids into the mitochondria, where they are broken down to produce energy. This condition can present in various forms, ranging from a severe neonatal form to a milder adult-onset form.

Symptoms and Forms

CPT II deficiency is categorized into three main forms: the lethal neonatal form, the severe infantile hepatocardiomuscular form, and the myopathic or adult form.

• The lethal neonatal form is characterized by severe metabolic crisis soon after birth, which can lead to liver failure, seizures, and often results in death within the first few days of life.
• The severe infantile hepatocardiomuscular form presents in early infancy with symptoms including hypoketotic hypoglycemia, cardiomyopathy, liver dysfunction, and muscle weakness. This form can be life-threatening but with early diagnosis and management, the prognosis can be significantly improved.
• The myopathic or adult form is the most common and the mildest form, typically manifesting during adolescence or early adulthood with muscle weakness, pain, and myoglobinuria (presence of muscle proteins in urine) especially after prolonged exercise, fasting, or illness. Episodes of rhabdomyolysis (breakdown of muscle tissue) can lead to kidney damage if not treated promptly.

Causes

CPT II deficiency is caused by mutations in the CPT2 gene, which provides instructions for making the carnitine palmitoyltransferase II enzyme. These mutations lead to a reduction in enzyme activity, which impairs the body's ability to oxidize long-chain fatty acids. The disorder is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Diagnosis

Diagnosis of CPT II deficiency typically involves a combination of clinical evaluation, family history, and specialized tests. Blood tests may reveal low blood sugar (hypoglycemia) and elevated muscle enzymes. The diagnosis can be confirmed through genetic testing to identify mutations in the CPT2 gene or by measuring the enzyme activity in muscle tissue.

Treatment

There is no cure for CPT II deficiency, but the condition can be managed with lifestyle adjustments and treatments aimed at preventing episodes of muscle pain and weakness. Management strategies include avoiding fasting, following a low-fat high-carbohydrate diet, and possibly supplementing with medium-chain triglycerides (MCT oil) and L-carnitine. During acute episodes, intravenous glucose may be necessary to prevent hypoglycemia.

Prognosis

The prognosis for individuals with CPT II deficiency varies depending on the form of the disorder. With early diagnosis and appropriate management, individuals with the myopathic form can lead relatively normal lives, although they may need to avoid certain triggers to prevent episodes of muscle weakness and pain. The prognosis for the severe infantile form has improved with advances in early detection and treatment, but it can still be life-threatening. The neonatal form remains the most severe, often resulting in early death.