Carnitine Palmitoyltransferase Deficiency

Carnitine palmitoyltransferase (CPT) deficiency is a group of disorders caused by defects in the enzymes CPT I or II. Type I is the most common human lipid myopathy. The metabolic myopathy can be triggered by effort, anesthesia/surgery, or stress and results in episodes of rhabdomyolysis and myoglobinuria.

Metabolic Myopathy and Carnitine Palmitoyltransferase Deficiency.

CPT deficiency is the most common metabolic cause of recurrent myoglobinuria.

Autosomal recessive. Three polymorphisms and more than 20 mutations have been identified in the CPT2 gene among patients with CPT II deficiency, with the responsible genetic defect mapped to 1p32. The mutations for the hepatic and muscle isoforms of CPT I are located on 11q13 and 22q13.3, respectively.

CPT I and II exist as two functionally distinct mitochondrial enzymes, embedded in the outer (CPT I) and inner (CPT II) mitochondrial membranes. Both are involved in facilitation of the transmembranous transport of fatty acids into the mitochondria.

Skin/muscle biopsy may be required to confirm the diagnosis. Prompt diagnosis can help to avoid risk factors and to prevent rhabdomyolysis and renal failure secondary to myoglobinuria.

CPT I exists in hepatic and muscle isoforms. To date, only hepatic CPT deficiency has been reported to cause clinical symptoms. In infancy, hepatic CPT I normally presents as recurrent hypoketotic, hypoglycemic coma triggered by fasting, exercise, intercurrent illness, cold stress, or a high-fat/low-carbohydrate diet. Additional findings during these acute episodes include metabolic acidosis, hepatomegaly with raised transaminases, hyperammonemia, and seizures. CPT I is normally not associated with cardiomyopathy or myopathy, although arrhythmias have been reported in pediatric patients, particularly in the infantile form. The results of liver function tests may remain pathologic for a few weeks before normalization is reestablished. CPT II deficiency is most commonly manifested in adulthood as intermittent episodes of myoglobinuria and myalgia occurring after exercise, fasting, sleep deprivation, (febrile) intercurrent illnesses, and anesthesia/surgery. Acute renal failure and cardiac arrest secondary to anesthesia-related rhabdomyolysis have been described. Between attacks, the patients may be asymptomatic, and electromyography, serum creatine kinase activity, and the response of serum lactate to ischemic exercise usually are normal. A rare infantile form of CPT II deficiency may present as fatal hypoglycemia with coma and/or with multiorgan involvement (cardiomyopathy, hepatic failure, and muscle weakness).

Liver and renal function and serum levels of electrolytes, carnitine, glucose, creatine kinase, and ammonia should be assessed preoperatively. Twelve-lead and/or Holter electrocardiography may be required if the history or examination suggests arrhythmias. In case of cardiomyopathy, echocardiography is recommended. The preoperative fasting period should be kept as short as possible. The recommendation is to start a dextrose-containing infusion at the beginning of the fasting period. Sedative and anxiolytic premedication may be helpful in reducing perioperative stress.

Acute deteriorations including coma and rhabdomyolysis may be precipitated by fasting, hypoglycemia, and perioperative stress. The minimum allowable duration of fasting should be considered, and patients should be given dextrose-containing intravenous fluids to prevent hypoglycemia. CPT-deficient patients may be susceptible to malignant hyperthermia: one group of researchers found that a subset of individuals in patients with known malignant hyperthermia phenotype had a primary deficiency of carnitine palmitoyltransferase and that others had a milder enzyme deficiency secondary to the primary defect in malignant hyperthermia. Regional anesthesia for intraoperative and postoperative analgesia significantly reduces the stress response and provides reasonable alternatives to general anesthesia and exposure to potential trigger agents. Dehydration should be avoided.

Malignant hyperthermia trigger agents should be avoided.

Carnitine Deficiency: A disorder caused by decreased carnitine concentrations in plasma and tissues preventing mitochondria from adequate beta oxidation. Primary and secondary defects have been described. The manifestations are cardiomyopathy, encephalopathy, and myopathy.

Myoadenylate Deaminase Deficiency: Either primary genetic disease affecting the muscle purine nucleotide metabolism or secondary to another neuromuscular or metabolic disease. It is found in up to 2% of muscle biopsies submitted for pathologic examination.

Phosphoglycerate Kinase Deficiency: A rare congenital enzymatic defect in glycolysis, mainly affecting the muscles and erythrocytes.

Reye Syndrome: May present similar to infantile CPT I. A potentially life-threatening, multifactorial syndrome resulting from a previous viral infection treated by aspirin and a genetic sensibility. Dehydration, intracranial hypertension, and liver failure must be considered. Presentation includes vomiting, lethargy, irrational behavior, and delirium. Tachypnea, jaundice, fever, and coma suggest end-stage disease. Reye syndrome usually appears 3 to 5 days after the onset of chickenpox rash.