Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency
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Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients representing the full clinical spectrum of disease. Severe and intermediate phenotypes show a clear correlation with biochemical indices and genetic analysis revealed causative mutations in most patients. Studies of mild phenotypes suggest a more complex interaction, with higher residual fatty acid oxidation, a wider range of CPT II activity (10–60%) but little evidence of genotype-phenotype correlation. Residual CPT II mutant protein from myopathic patients shows thermal instability at 41°C. The common 'polymorphisms' V3681 and M647V are strikingly overrepresented in the myopathic patients, the implication being that they may significantly influence the manifestation of clinical disease and could therefore potentially be considered as a susceptibility variants. Among myopathic individuals, males comprised 88! of patients, suggesting increased susceptibility to clinical disease. A small number of symptomatic patients appear to have significant residual CPT II activity (42–60%) The synergistic interaction of partial deficiencies of CPT II, muscle adenosine monophosphate deaminase and possibly other enzymes of muscle energy metabolism in the aetiology of episodic myopathy deserves wider consideration.
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- Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency
Journal of Inherited Metabolic Disease
Volume 26, Issue 6 , pp 543-557
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- Author Affiliations
- 1. Department of Clinical Chemistry, Sheffield Children's Hospital, UK
- 2. Department of Clinical Biochemistry, Sheffield Children's Hospital, Sheffield, S10 2TH, UK
- 3. Department of Molecular Genetics, Sheffield Children's Hospital, UK
- 4. Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, London
- 5. Neurometabolic Unit, National Hospital, London
- 6. Research Unit for Molecular Medicine and Institute for Human Genetics, Aarhus University, Aarhus, Denmark
- 7. James Spence Institute of Child Health, Royal Victoria Hospital, Newcastle, UK
- 8. Dubowitz Neuromuscular Centre, Hammersmith Hospital, London
- 9. School of Clinical Neurosciences, University of Newcastle, UK