This disease is also inherited as an autosomal recessive trait and the gene encoding carnitine palmitoyltransferase (CPT) has been identified. There are three types: types I, IIA, and IIB. Type I is the most common. It affects males predominantly, beginning in the second decade of life. Attacks of myalgia, cramps, and muscle weakness, “tightness,” and stiffness are precipitated by sustained (although not necessarily intense) exercise and less often by a prolonged period of fasting. Fever, anesthesia, drugs, emotional stress, and cold have been additional but rare precipitating events. The attacks vary greatly in frequency. They are usually accompanied by myoglobinuria, with resultant renal failure in about one-fourth of cases (DiMauro et al, 1973). Rest does not abort the attacks and, once initiated, there is no second-wind phenomenon. There are no warning signs of an impending attack. Any muscle group may be affected. Persistence of weakness after an attack is uncommon. Serum CK rises to high levels not only during attacks but also after vigorous exercise without myoglobinuria. A mild form is more likely to occur in females.
In type I deficiency, necrosis of muscle fibers, particularly type I fibers, occurs during attacks, followed by regeneration. Between attacks, the muscle appears normal. In type IIA, lipid bodies accumulate in the liver, and in type IIB, excess lipid is detected in heart, liver, kidneys, and skeletal muscle.
CPT is either undetectable or greatly reduced in muscle, and assays are now available for the measurement of CPT I and II in circulating lymphocytes and cultured fibroblasts. Testing for the mutation is available.
Treatment A high-carbohydrate, low-fat diet, ingestion of frequent meals, and additional carbohydrate before and during exercise appear to reduce the number of attacks. Patients need to be instructed about the risks of prolonged exercise and skipped meals. Recently, the use of bezafibrate, a drug used for dyslipidemia, has been helpful in patients with mild CPT II.
This is occasionally the result of severe dietary deprivation or impaired hepatic and renal function. Such instances have been observed in patients with alcoholic–nutritional diseases and kwashiorkor, in premature infants receiving parenteral nutrition, in patients with chronic renal failure undergoing dialysis, and rarely, as a complication of valproate therapy. However, most cases of systemic carnitine deficiency are a result of defects of beta-oxidation, described as follows.
Carnitine acylcarnitine translocase deficiency This condition causes muscular weakness, cardiomyopathy, hypoketotic hypoglycemia, and hyperammonemia, which develop in early infancy and usually lead to death in the first month of life.
Long-chain acyl-CoA dehydrogenase deficiency (ACLDVL mutation) The presentation is in infancy, with recurrent episodes of fasting hypoglycemic coma, muscle weakness, and myoglobinuria, and sometimes sudden death. Survivors may develop a progressive myopathy. Administration of carnitine improves the cardiac disorder and prevents metabolic attacks.
Medium-chain acyl-CoA dehydrogenase deficiency (ACADM mutation) This is a cause of SIDS and a Reye-like syndrome. About half of survivors develop a lipid-storage myopathy in childhood or adult life. The abnormal gene has been mapped to chromosome 1p31. Oral l- carnitine may be of therapeutic value.
Short-chain acyl-CoA dehydrogenase deficiency This myopathy in a limb-girdle distribution may appear initially in older children and adults, or it may follow episodic metabolic disorders in infancy.