Mitochondrial Fatty Acid Oxidation Disorders: Laboratory Diagnosis, Pathogenesis, and the Complicated Route to Treatment.
Ronald J A WandersGepke VisserSacha FerdinandusseFrederic M VazRiekelt H L HoutkooperPublished in: Journal of lipid and atherosclerosis (2020)
Mitochondrial fatty acid (FA) oxidation deficiencies represent a genetically heterogeneous group of diseases in humans caused by defects in mitochondrial FA beta-oxidation (mFAO). A general characteristic of all mFAO disorders is hypoketotic hypoglycemia resulting from the enhanced reliance on glucose oxidation and the inability to synthesize ketone bodies from FAs. Patients with a defect in the oxidation of long-chain FAs are at risk to develop cardiac and skeletal muscle abnormalities including cardiomyopathy and arrhythmias, which may progress into early death, as well as rhabdomyolysis and exercise intolerance. The diagnosis of mFAO-deficient patients has greatly been helped by revolutionary developments in the field of tandem mass spectrometry (MS) for the analysis of acylcarnitines in blood and/or urine of candidate patients. Indeed, acylcarnitines have turned out to be excellent biomarkers; not only do they provide information whether a certain patient is affected by a mFAO deficiency, but the acylcarnitine profile itself usually immediately points to which enzyme is likely deficient. Another important aspect of acylcarnitine analysis by tandem MS is that this technique allows high-throughput analysis, which explains why screening for mFAO deficiencies has now been introduced in many newborn screening programs worldwide. In this review, we will describe the current state of knowledge about mFAO deficiencies, with particular emphasis on recent developments in the area of pathophysiology and treatment.
Keyphrases
- fatty acid
- end stage renal disease
- hydrogen peroxide
- skeletal muscle
- oxidative stress
- high throughput
- newly diagnosed
- tandem mass spectrometry
- mass spectrometry
- ejection fraction
- type diabetes
- prognostic factors
- multiple sclerosis
- heart failure
- healthcare
- peritoneal dialysis
- public health
- liquid chromatography
- insulin resistance
- high performance liquid chromatography
- high intensity
- ms ms
- single cell
- simultaneous determination
- patient reported
- combination therapy
- smoking cessation