Novel mutations in the gene encoding very long-chain acyl-CoA dehydrogenase identified in patients with partial carnitine palmitoyltransferase II deficiency.

Twenty-six patients with clinical symptoms of adult onset carnitine palmitoyltransferase II (CPTII) deficiency were examined. All patients had skeletal muscle CPTII enzyme activity levels indicative of heterozygosity for CPT2 mutations, however sequence analysis identified no pathogenic mutations within the CPT2 gene. Because the reaction product of CPTII is the substrate for very long-chain acyl-CoA dehydrogenase (VLCAD), we examined the ACADVL gene in these patients by sequence analysis. Missense mutations within the ACADVL gene were identified in 3 of the patients. The locations of the altered amino acid residues within the crystal structure of VLCAD are on the surface of the molecule and may be involved in interactions with neighboring molecules. These findings support the importance of considering that mutations may be present in the ACADVL gene when a significant partial deficiency is found in CPTII activity, but no mutations in the CPT2 gene can be identified.