Lactic acidosis in long‐chain fatty acid β‐oxidation disorders

Among the many disorders of fatty acid β‐oxidation known today, the disorders of long‐chain fatty acid oxidation are the most severe and life‐threatening. One remarkable abnormality, not observed in, for instance, medium‐chain acyl‐CoA dehydrogenase deficiency, is the moderate to severe lactic acidaemia in long‐chain fatty acid β‐oxidation‐deficient patients, suggesting that oxidation of pyruvate is also compromised. In order to understand the underlying basis of the lactic acidaemia in these patients, we have studied the formation of L‐lactate and pyruvate in cultured skin fibroblasts incubated with D‐glucose. All long‐chain fatty acid β‐oxidation‐deficient cell lines studied were found to show a moderate elevation of lactate when compared with control and medium‐chain acyl‐CoA dehydrogenase‐deficient fibroblasts. Interestingly, differences were found between cells deficient in long‐chain 3‐hydroxyacyl‐CoA dehydrogenase and very‐long‐chain acyl‐CoA dehydrogenase, suggesting that saturated acyl‐CoA esters and their 3‐hydroxyacyl‐CoA derivatives affect pyruvate metabolism differently.