L-carnitine deficiency, the adult form of carnitine palmitoyltransferase (CPT) II deficiency, has been labeled as the most common lipid myopathy in humans. This autosomal recessively inherited disease may be even more prevalent than generally believed due to under-recognition of the disorder.
CPT II is associated with the inner mitochondrial membrane. It works 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. Individuals with this disorder may be symptom-free until they are exposed to prolonged exercise, fasting, extremes in temperature, viral infection or statin drugs.
Being of genetic origin, this condition is often first identified in children. However we now understand that variant forms of this metabolic disease are often almost completely subclinical with initial presentation often in adults and the elderly due to the relatively increased stress of exercise and temperature loading.
In Muscle and Nerve 2006, Vladutiu GD and others, studying genetic risk factors underlying myopathies, including those associated with statin therapy, reported a far higher prevalence of underlying metabolic muscle diseases than expected in the general population.
The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease, a related condition, was increased 13 and 20-fold, respectively, over expected general population frequencies.
In 52% of muscle biopsies from patients, all of whom were adults, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. In subjects whose symptoms were associated with the use of statin drugs, variable persistent symptoms persisted in 68% of patients despite cessation of therapy, particularly in the elderly.
The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for severe myopathic outcomes and even rhabdomyolysis in certain groups.
There are many people with the disorder who are completely unaware of its existence until they experience severe statin associated myopathy or rhabdomyolysis.
At the other end of the spectrum there are people with mild episodic symptoms who have never had a major attack and wonder if they have a disease at all or if their symptoms of muscle pain on effort are "all in their mind."
The results of this study reveal that the frequency of subclinical forms in the adult and elderly population far exceeds juvenile presentation.
More than 20 different mutations have been identified in the CPT2 gene among patients with CPT II deficiency and many other mutations are yet to be identified.
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.
The most important consideration in CPT II deficiency is that most of this condition remains subclinical and therefore unrecognized. A history of muscle pain following exercise is helpful but far from definitive.
The use of statin drugs with their natural tendency to inhibition of CoQ10 has led to the identification of many carriers of this genetic trait in adults and elderly who otherwise never would have been discovered.
One of the best tests for this condition is response to the supplement, L-carnitine. A positive response establishes the diagnosis until more definitive studies can be done. L-carnitine and CPT plays a major role in the metabolism of fatty acids by our mitochondria.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated November 2015