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Mitochondrial Fatty Acid Oxidation Disorders: Laboratory Diagnosis, Pathogenesis, and the Complicated Route to Treatment

Journal of Lipid and Atherosclerosis 2020년 9권 3호 p.313 ~ 333
Wanders Ronald J. A., Visser Gepke, Ferdinandusse Sacha, Vaz Frederic M., Houtkooper Riekelt H.,
소속 상세정보
 ( Wanders Ronald J. A. ) - University of Amsterdam Laboratory Genetic Metabolic Diseases
 ( Visser Gepke ) - University of Amsterdam Laboratory Genetic Metabolic Diseases
 ( Ferdinandusse Sacha ) - University of Amsterdam Laboratory Genetic Metabolic Diseases
 ( Vaz Frederic M. ) - University of Amsterdam Laboratory Genetic Metabolic Diseases
 ( Houtkooper Riekelt H. ) - University of Amsterdam Laboratory Genetic Metabolic Diseases

Abstract


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.

키워드

Fatty acid oxidation disorders; Fatty acid oxidation; Mitochondria; Cardiomyocytes; Acylcarnitines; Inborn errors of metabolism

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