Carnitine palmitoyltransferase II deficiency - CPT II- CPT2 gene

Carnitine palmitoyl transferase II (CPT II) deficiency is a hereditary metabolic disease that affects the oxidation of fatty acids for energy, especially during fasting periods. There are three main types of CPT II deficiency: a lethal neonatal form, a severe childhood hepatocardiomuscular form and a myopathic form.

The lethal neonatal form of CPT II deficiency becomes evident shortly after birth. Children with this form develop respiratory failure, seizures, liver failure, cardiomyopathy and arrhythmias. Affected individuals also have hypoglycemia and a low level of ketones, which occur during the breakdown of fatty acids. Together, these signs are called hypocetosic hypoglycemia. In many cases, the brain and kidneys are also structurally abnormal. Newborns with the lethal neonatal form of CPT II deficiency usually live between a few days to a few months.

The severe childhood hepatocardiomuscular form affects the liver, heart and muscles. Signs and symptoms usually appear in the first year of life. This form is characterized by recurrent episodes of hypocetosic hypoglycemia, seizures, hepatomegaly, cardiomyopathy and arrhythmias. Problems related to this type of deficiency can be caused by periods of fasting or viral infections. Individuals with severe childhood hepatocardiomuscular form are at risk of liver failure, neuronal damage, coma and sudden death.

The myopathic form is the least severe type of CPT II. This form is characterized by recurrent episodes of myalgia and rhabdomyolysis. The destruction of muscle tissue releases myoglobin, which is processed by the kidneys and released into the urine (myoglobinuria). This protein can also damage the kidneys and, in some cases, lead to kidney failure. Episodes of myalgia and rhabdomyolysis can be triggered by exercise, stress, exposure to extreme temperatures, infections or fasting. The first episode usually occurs during childhood or adolescence. Most people with myopathic form have no signs or symptoms of the disease between episodes.

CPT II deficiency is due to alterations in the sequence of the CPT2 gene (carnitine palmitoyl transferase 2), which is found in the short arm of chromosome 1 (1p32), and encodes the carnitine palmitoyl transferase II enzyme, essential for oxidation of fatty acids.

More than 70 mutations in the CPT2 gene have been described in people with CPT II deficiency. Mutations in the CPT2 gene reduce the activity of carnitine palmitoyl transferase 2. The absence of this enzyme prevents oxidation of long-chain fatty acids and as a consequence the appearance of symptoms of CPT II deficiency. Long-chain fatty acids and acylcarnitins can also accumulate in cells and damage the liver, heart and muscles. Mutations that result in excessive reduction of the enzyme will result in lethal neonatal forms and severe childhood hepatomuscular form, while those that reduce enzymatic activity slightly are responsible for the less severe myopathic form. The most common mutations of the CPT2 gene are those caused by substitution of serine with leucine at position 113 (Ser113Leu or S113L) in the enzyme. This mutation represents about 60% of the mutations that lead to the development of the myopathic form.

This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Carnitine palmitoyltransferase II deficiency -CPT II-, by means of the complete PCR amplification of the exons of the CPT2 gene, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).