title: Myopathic form of very-long chain acyl-coa dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.
abstract: In a 14-year-old Japanese girl, manifested recurrent myalgia with elevated serum creatine kinase after moderate exercise became evident, and she was diagnosed as having a myopathic form of very-long chain acyl-CoA dehydrogenase deficiency. Her first clinical symptom of the disease was evident when she was 6 y of age. She had never had hypoglycemic attacks, and hepatomegaly and cardiomyopathy were absent. The diagnosis was suspected on the basis of the urinary organic acid profile after a 36-h fast, long-chain fatty acid-loading test, and the blood acylcarnitine profile. Acyl-CoA dehydrogenase activity with palmitoyl-CoA as a substrate was severely decreased in her fibroblasts, and the amount of very-long chain acyl-CoA dehydrogenase protein was reduced. She was a compound heterozygote of A416T from her father and R450H from her mother. Transient expression of mutant A416T cDNA retained a significant residual acyl-CoA dehydrogenase activity of 10% and 20% normal at 37 degrees C and 30 degrees C, respectively. Specific activity of A416T mutant protein was calculated to be one fifth that of control. In the case of R450H mutant expression, a low residual acyl-CoA dehydrogenase activity of 5% normal was detected at 30 degrees C although significant activity was absent at 37 degrees C. The R450H protein was not detected at 37 degrees C but was clearly detected at one fourth the normal amount at 30 degrees C. These results indicate that both mutations were temperature-sensitive mild mutations, the result being the mildest phenotype of very-long chain acyl-CoA dehydrogenase deficiency.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Gifu 500-8075, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukao
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Orii
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: N
authors.initials: N
authors.lastname: Kondo
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism*; D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D005260:Female; D006801:Humans; D009135:Muscular Diseases / Q000201:enzymology* / Q000235:genetics; D009154:Mutation
chemical_list: D017931:DNA Primers; D044942:Acyl-CoA Dehydrogenase, Long-Chain