CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency

• Published in: Molecular genetics and metabolism 2008-08, Vol.94 (4), p.422-427
• Main Authors: Isackson, Paul J., Bennett, Michael J., Lichter-Konecki, Uta, Willis, Mary, Nyhan, William L., Sutton, V. Reid, Tein, Ingrid, Vladutiu, Georgirene D.
• Format: Article
• Language: English
• Subjects: Amino Acid Metabolism, Inborn Errors - enzymology; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Sequence; Amino Acid Substitution; Base Sequence; Carnitine O-Palmitoyltransferase - chemistry; Carnitine O-Palmitoyltransferase - deficiency; Carnitine O-Palmitoyltransferase - genetics; Expanded newborn screening; Fatal Outcome; Fatty acid oxidation defect; Female; Genotype/phenotype correlation; Humans; Infant, Newborn; Male; Metabolism, Inborn Errors - enzymology; Metabolism, Inborn Errors - genetics; Molecular diagnostics; Muscular Diseases - enzymology; Muscular Diseases - genetics; Mutation; Phenotype
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2008.05.002

Three distinct clinical manifestations of carnitine palmitoyltransferase II (CPT II) deficiency have been defined including a mild adult onset myopathy, a severe infantile disorder and a lethal neonatal form. In this study we have examined the genomic DNA of five patients, 3 with the lethal neonatal form and 2 with the severe infantile form of the disease and identified two disease-causing mutations in the CPT2 gene for each patient, three of which are novel. In addition, based on currently available structural, biochemical and clinical data, we have classified all 64 known disease-causing mutations into groups with different predicted phenotypes depending on their CPT2 allelic counterparts.