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Carnitine Palmitoyltransferase (CPT) II deficiency has been labeled as the most common lipid myopathy in humans. This autosomal recessively inherited disease has earned this distinction because the other lipid disorders with muscle symptoms are very rare. CPT II deficiency may be even more prevalent than first believed due to under-recognition of the disorder. Many people with the disorder are completely unaware of its existence. The disorder has even been called "benign" in some scientific reports which could not be farther from the truth among individuals who have experienced life-threatening kidney failure following a severe episode of Rhabdomyolysis (trigger-induced muscle breakdown).

At the other end of the spectrum there are people with mild symptoms who have never have had a major attack and wonder if they have a disease at all or if their symptoms are "all in their mind." They may never have gone to a physician for evaluation or if they did, their doctor may not have known enough about the disease to recognize it or how to treat it. Many people have been initially misdiagnosed as having other disorders, such as fibromyalgia or chronic fatigue syndrome, before arriving at the correct diagnosis of CPT II deficiency. Before discussing the characteristics of the disease and which individuals may be at risk for having it, it is important to understand what role CPT II and closely related enzymes normally play in the human body.

Cell Function & CPT Symptoms
CPT exists as two genetically and functionally distinct mitochondrial enzymes (CPT I and CPT II). CPT I is embedded in the outer mitochondrial membrane and CPT II is associated with the inner mitochondrial membrane. They work together with carnitine-acylcarnitine translocase, an inner mitochondrial membrane Enzyme, to facilitate the transport of lipids (fatty acids) across these membranes and into the mitochondrial matrix where they ultimately are converted to energy in the form of ATP. This conversion of fatty acids occurs when the body runs out of usable carbohydrates for energy and must turn to fats for energy. With CPT deficiency, the body cannot effectively turn the fatty acids into energy, thus, the body looks for other sources of energy. Many times the body attacks muscle tissue for its energy needs causing extreme muscle soreness.Myoglobinuria occurs when the broken down muscle tissue is passed out through urine. However, if the kidneys cannot process the massive amount of broken down muscle tissuerhabdomyolysis can occur damaging the kidneys.

Individuals with this disorder may be symptom-free until they are exposed to:

prolonged exercise
fasting
extremes in temperature
viral infection
sleep deprivation
general anesthesia during surgery
or other triggers
Even though the disorder is called an "adult-onset" disease, it has been reported in people of all ages including young children. Not only does the age of onset vary in CPT II deficiency but also there has been a wide range of symptoms reported among affected individuals.

Symptoms include:

Severe muscle pain that occurs during exercise or several hours afterward
Muscle stiffness and tenderness for hours or days
The presence of dark-colored urine caused by the release of Myoglobin from damaged muscle tissue
Rhabdomyolysis
Diagnosis & Treatment
The diagnosis of CPT can be a long and ardous process. Patients usually are subjected to a battery of tests and procedures to rule out any other possible factors before CPT is even considered. Once all other diseases have been discounted a Muscle Biopsy is ordered. In the recent past, CPT II deficiency could only be diagnosed by biochemical analysis of a muscle biopsy. While this remains the best specimen for a definitive diagnosis, the enzyme's activity can also be measured in white blood cells and a mutation screening can be performed for the common mutations in white blood cells or cheek cells, both relatively noninvasive specimens. The problem with mutation screening for virtually any genetic disorder is that one cannot be certain that all mutations have been identified. However, a screen for a panel of 6 known mutations in the CPT2 gene rules out over 90% of causative mutations.

The treatment of CPT II deficiency is variable and often patient-specific considering the wide variation in symptoms and lifestyles. There are certain things affected individuals can do to prevent symptoms. Most try to avoid the triggers such as prolonged vigorous exercise, fasting, and extremes in temperature. If they need to have surgery with general anesthesia, they alert their physician to the need for alternative anesthetics that do not trigger symptoms, plus most people with CPT II deficiency wear Medic Alert tags describing their condition and the associated risks. Individuals with CPT II deficiency try to keep their water intake high, especially if they are athletes, and keep sources of simple carbohydrates handy such as Gatorade and Powerade. However, there are specific treatment regimens for CPT II-deficient patients, including the administration of MCT Oil (medium-chain triglycerides) or carnitine that should be established on a case by case basis under the supervision of a metabolic physician and nutritionist. Patients should not try to treat themselves without the involvement of these professionals because they may have adverse or suboptimal effects from certain treatments.

In spite of the fact that there is no cure for CPT II deficiency, it is a manageable disease in most cases. It is important that primary care physicians are informed about this disorder and its manifestations so that they can recognize the symptoms, provide genetic testing for a diagnosis and treatment. Frequently patients who remain undiagnosed wonder if their symptoms are imagined or exaggerated because of the chronic nature of the disease.

References:

Matter Over Mind: The Realities of a Common Muscle Disease by Georgirene D. Vladutiu, Ph.D.
Fundamental Differences by Georgirene D. Vladutiu, Ph.D. Published on The Spiral Notebook Website
Facts About Metabolic Diseases of the Muscle by the Muscular Dystrophy Association
Cell image courtesy of the Muscular Dystrophy Association http://www.mda.org