Fatal hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency: Clinical, biochemical, and pathological studies on three subjects withthis recently identified disorder of mitochondrial beta-oxidation

This report describes the clinical, biochemical, and pathological findings in three infants with hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydr ogenase (SCHAD) deficiency, a recently recognized disorder of the mitochond rial oxidation of straight-chain fatty acids. Candidate subjects were ident ified from an ongoing study of infant deaths. SCHAD analysis was performed on previously frozen liver and skeletal muscle on subjects with a character istic urine organic acid profile. Autopsy findings were correlated with the biochemical abnormalities. Enzyme analysis in liver revealed marked defici ency in SCHAD with residual activities of 3-11%. All subjects had normal ac tivity in skeletal muscle. However, Western blot analysis of SCHAD revealed an identical truncated protein in both liver and muscle from one patient, suggesting that SCHAD is similar in liver and muscle and that the normal ac tivity in muscle may be due to other enzymes with C4 activity. Autopsy find ings revealed marked steatosis and a muscle pattern consistent with spinal muscular atrophy in one patient. Lipid storage was less pronounced in one p atient and not detected in the third patient who had a well-documented hist ory of recurrent hypoglycemia. This is the initial pathological characteriz ation of this enzyme defect, and our observations suggest that SCHAD defici ency is a very severe disorder contributing to early infant death.