Clinical Information

Mitochondrial fatty acid beta-oxidation plays an important role in energy production, particularly in skeletal and heart muscle, and in hepatic ketone body formation. Disorders of fatty acid oxidation (FAO) are characterized by hypoglycemia, hepatic dysfunction, encephalopathy, skeletal myopathy, and cardiomyopathy. Most FAO disorders have a rather similar presentation and their biochemical diagnosis can, at times, be difficult. Commonly used metabolite screens such as urine organic acids, plasma acylcarnitines, and fatty acids are influenced by dietary factors and the clinical status of the patient. This often leads to incomplete diagnostic information or even false-negative results. Enzyme assays are limited to 1 enzyme per assay, and molecular assays for common mutations are limited by the frequent occurrence of compound heterozygous patients with uncommon, private mutations that must be distinguished from unaffected carriers. Furthermore, neither specific enzyme assays nor molecular genetic testing is available for all of the known defects. The purpose of the in vitro probe assay is to offer screening for several defects of FAO and organic acid metabolism under controlled laboratory conditions using fibroblast cultures.