How Genes Meet Diet in LCHAD Deficiency: Nutrigenomics of Fatty Acid Oxidation Disorder.

Mitochondrial long-chain fatty acid β-oxidation supplies energy to the heart, liver, and skeletal muscle. Impairment of this process due to a block at the step catalyzed by long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) leads to bioenergetic failure, manifesting as hypoglycemia, recurrent rhabdomyolysis, cardiomyopathy, and hepatic dysfunction. Accumulation of toxic intermediates-long-chain 3-hydroxyacyl-CoAs and the corresponding 3-hydroxyacylcarnitines-contributes to pigmentary retinopathy and peripheral neuropathy. Early diagnosis and careful dietary management can reduce life-threatening decompensation in childhood and improve survival into adulthood. This review examines the genetics of human LCHAD deficiency, describes its multisystem complications, and outlines nutritional strategies used to bypass the enzymatic block. We also explore nutrigenomic signals elicited by dietary treatment in LCHAD deficiency.