Clinical characteristics: Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form (which is usually mild and can manifest from infancy to adulthood). While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females.
Diagnosis/testing: The diagnosis of CPT II deficiency is established in a proband by the finding of reduced CPT enzyme activity in muscle or the identification of biallelic pathogenic variants in CPT2 on molecular genetic testing.
Management: Treatment of manifestations: High-carbohydrate (70%) and low-fat (<20%) diet to provide fuel for glycolysis; use of carnitine to convert potentially toxic long-chain acyl-CoAs to acylcarnitines; avoidance of known triggers. Prevention of primary manifestations: Infusions of glucose during intercurrent infections to prevent catabolism; frequent meals; avoiding extended fasting and prolonged exercise. Prevention of secondary complications: Providing adequate hydration during an attack of rhabdomyolysis and myoglobinuria to prevent renal failure. Agents/circumstances to avoid: Valproic acid, general anesthesia, ibuprofen, and diazepam in high doses. Evaluation of relatives at risk: If the pathogenic variants have been identified in an affected family member, molecular genetic testing of at-risk relatives can reduce morbidity and mortality through early diagnosis and treatment; if the pathogenic variants in the family are not known, screening for alterations in acylcarnitines may be of use in identifying other affected family members.
Genetic counseling: CPT II deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are usually asymptomatic; however, manifesting carriers have been reported. Prenatal diagnosis for pregnancies at increased risk for one of the severe forms of the disease is possible either by molecular genetic testing of CPT2, if the two pathogenic variants in the family are known, or by assay of CPT II enzyme activity.
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