Carnitine palmitoyltransferase 2 deficiency
Description, Causes and Risk Factors:
An enzyme that reversibly forms acylcarnitines and coenzyme A from carnitine and acylcoenzyme A (often, palmitoyl-CoA); important in fatty acid oxidation. Deficiency of isozyme I results in ketogenesis with hypoglycemia; deficiency of isozyme II affects primarily skeletal muscle.
The mitochondrial oxidation of fatty acids is the main source of energy for muscle during prolonged exercise and during fasting. The carnitine palmityltransferase (CPT) enzyme system is essential for the transfer of fatty across the mitochondrial membrane. This system including CPT-1 in the outer mitochondrial membrane and Carnitine palmitoyltransferase 2 and carnitine acylcarnitine translocase in the inner mitochondrial membrane.
Mutations in the Carnitine palmitoyltransferase 2 gene cause CPT-2 deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 2. This enzyme is essential for fatty acid oxidation, which is the multi-step process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids (LCFAs) must be attached to a substance known as carnitine to enter mitochondria. Once these fatty acids are inside mitochondria, carnitine palmitoyltransferase 2 removes the carnitine and prepares them for fatty acid oxidation. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.
Carnitine palmitoyltransferase 2 deficiency is an autosomal recessive trait, gene locus 1p32/1q32 with three main phenotypes. The most severe phenotype is a fatal nonketotic-hypoglycemic encephalopathy of infants in which CPT-2 is deficient in several organs. Exercise intolerance with myoglobinuria characterizes the less severe phenotype of Carnitine palmitoyltransferase 2 deficiency of muscle. CPT-2 deficiency is the most common metabolic disorder of skeletal muscle. The phenotype variations in the muscle disease caused by CPT-2 deficiency probably relate to the type of molecular defect and to superimposed environmental factors such as prolonged fasting, exercise, cold exposure, and intercurrent illness.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
People with Carnitine palmitoyltransferase 2 deficiency are at risk of malignant hyperthermia.
CPT-2 deficiency is rare. The lethal neonatal form has been documented in 13 families, while the severe infantile hepatocardiomuscular form has been studied in 20 families. There are more than 200 known cases of the myopathic form, however scientists believe this form often goes unrecognized, particularly in its mildest cases, and may be more common than studies have indicated.
Age of onset of symptoms ranges from 1 year to adulthood. In 70% of cases, the disease starts by age 12 years, and in most cases, the disease starts between 13 and 22 years of age. Performing heavy exercise of short duration poses no difficulty. However, pain, tenderness, and swelling of muscles develop after sustained aerobic exercise. Severe muscle cramps as in myophosphorylase deficiency, do not occur. Associated with the pain may be actual muscle injury characterized by an increased serum creatine kinase (SCK) concentration and myoglobinuria. Muscle injury may also accompany periods of prolonged fasting especially in patients of low-carbohydrate, high-fat diets.
The clinical features suggest the diagnosis and measuring concentration of CPT-2 in muscle provides confirmation. Muscle histology is usually normal between attacks.Tandem mass spectrometry: non-invasive, rapid method; a significant peak at C16 is indicative of generalized Carnitine palmitoyltransferase 2 deficiency.
- Enzymatic activity studies in fibroblasts and/or lymphocytes.
- Laboratory findings: most patients have low total and free carnitine levels and high acylcarnitine:free carnitine ratios. Adult patients often have serum and/or urine screen positive for the presence of myoglobin and SCK and transaminase levels 20-400x higher than normal levels during an attack.Signs of metabolic acidosis and significant hyperammonemia have been reported in infantile and neonatal cases.
There is no cure for Carnitine palmitoyltransferase 2 deficiency, and very little can be done to help infants and children with the more severe forms of the disease, other than to treat symptoms as they arise.
For people with the myopathic form, there are recommendations that can help prevent attacks. Frequent meals with a high-carbohydrate, low-fat diet can be helpful. Supplements of carnitine may also be recommended. During infection, a physician may recommend infusions of glucose. Circumstances to avoid include strenuous exercise, prolonged fasting, and extreme cold.
During attacks, a person with the myopathic form of CPT-2 deficiency should drink plenty of fluids to avoid kidney problems.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.