A variable myopathy associated with heterozygosity for the R503C mutation in the carnitine palmitoyltransferase II gene.

Adult-onset carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disease characterized by muscle pain and stiffness with rhabdomyolysis and myoglobinuria in severe cases. Exercise, fasting, viral infection, anesthesia, or extremes in temperature may trigger symptoms. A 54-year-old woman exhibited a 35-year history of progressive weakness and myopathic symptoms. CPT II activity in the patient's lymphoblasts, cultured skin fibroblasts, and skeletal muscle was reduced to 47, 43, and 13% of normal, respectively. Respiratory chain enzymes were also reduced in muscle ranging from 22 to 49% of their respective normal reference means. beta-oxidation enzymes in fibroblasts ranged from 29 to 63% of normal. The patient, her father, and her 26-year-old son were all heterozygous for the R503C mutation. The patient's son has a lifelong history of myopathic symptoms while his grandfather only had mild weakness during childhood. Analysis of the V368I and M647V polymorphisms in the CPT2 gene showed that the mutant allele is linked to 368I and 647M in this family and that the normal allele is linked to 647V in the affected patient and her son, and to 647M in the patient's father. While the variability in CPT2 gene haplotypes may contribute to the phenotypic complexities in this family, it is also possible that an additional gene defect in the transport of mitochondrial proteins contributes to the complex phenotype in the patient. We present biochemical and molecular evidence for vertical transmission of a variable myopathy caused by heterozygosity for a single mutation, R503C, in the CPT2 gene.