Carnitine Palmitoyl Transferase Ii Deficiency, Myopathic Form

The myopathic form of carnitine palmitoyltransferase II (CPT II) deficiency, an inherited metabolic disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the most common and the least severe form of CPT II deficiency (see this term).

Epidemiology

About 300 cases of the myopathic form have been reported in the literature, but this number may under-estimate the disease prevalence.

Clinical description

The age of onset varies between 1 and 61 years of age with 70% of cases first presenting in childhood. The disease is more common in men, probably reflecting an ascertainment bias related to exposure to prolonged exercise. The clinical manifestations are characterized by recurrent attacks of rhabdomyolysis, muscle pain, and weakness triggered usually by prolonged physical exercise and sometimes exacerbated by extremes in temperature; episodes may also be provoked or exacerbated by prolonged fasting, such as may occur with intercurrent viral illness. Episodes of rhabdomyolysis may be associated with extreme elevation of serum creatine phosphokinase (CPK) and myoglobinuria (75% of cases) and can lead to renal failure (in 8-25% of cases, but rarely requiring dialysis). Patients are asymptomatic between episodes of rhabdomyolysis.

Etiology

Several missense mutations in the CPT2 gene result in the myopathic form of CPT II deficiency. In Caucasians, the most frequent mutation (60%) is the p.Ser113Leu mutation, which impairs enzyme stability.

Diagnostic methods

The diagnosis is made by an initial tandem mass spectrometry of serum/plasma acylcarnitines followed by mutation analysis and measurements of CPT2 enzyme activity in fresh circulating lymphocytes, muscle or fibroblasts.

Differential diagnosis

The differential diagnosis should include McArdle disease, Duchenne muscular dystrophy, cytochrome c oxidase deficiency (see these terms), complex II deficiency, complex III deficiency and rhabdomyolysis due to excessive exercise, infections, autoimmune reactions or drug-related neuroleptic syndrome among others.

Genetic counseling

Transmission is autosomal recessive. If the disease-causing mutations are identified in an affected individual, early diagnosis by molecular genetic testing can be offered to at-risk relatives to reduce morbidity and mortality.

Management and treatment

Treatment is based on avoidance of prolonged fasting (>12 hr) and a low-fat and high-carbohydrate diet combined with exercise restriction in order to avoid muscle pain and rhabdomyolysis. L-carnitine administration and anaplerotic diet therapy with triheptanoin have been suggested for treatment of the disease; however benefits have not been proven.

Prognosis

The myopathic form of CPT II has a good prognosis.