Retrospective Biochemical Screening of Fatty Acid Oxidation Disorders in Postmortem Livers of 418 Cases of Sudden Death in the First Year of Life

J Pediatr. 1998 Jun;132(6):924-33. doi: 10.1016/s0022-3476(98)70385-3.

Abstract

Objective: Fatty acid oxidation (FAO) disorders are frequently reported as the cause of sudden and unexpected death, but their postmortem recognition remains difficult. We have devised a biochemical protocol in which informative findings in liver tissue are microvesicular steatosis, elevated concentrations of C8-C16 fatty acids, glucose depletion, and low carnitine concentration.

Study design: We analyzed 27 cases representing five FAO disorders and compared the results with those obtained in a retrospective blinded analysis of 418 cases of sudden infant death (313 SIDS, 45 infections, and 34 accidents and abuse).

Results: All cases of accidents and abuse correctly tested negative. Among the others, 25 (6%) showed at least two abnormal findings. Of these, 14 closely matched the biochemical profiles seen in specific FAO disorders. These included 2 cases with medium-chain acyl-CoA dehydrogenase deficiency, 4 cases consistent with glutaric acidemia type 2, 4 cases with either very long-chain acylcoenzyme A dehydrogenase deficiency or long-chain 3-hydroxy-acyl-coenzyme A dehydrogenase deficiency, and 4 cases predicted to be affected with carnitine uptake defect.

Conclusion: The results of this study support the view that approximately 5% of all cases of sudden infant death are likely caused by an FAO disorder.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency
  • Acyl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency
  • Carnitine / metabolism
  • Case-Control Studies
  • Fatty Acids / metabolism*
  • Female
  • Glutarates / blood
  • Humans
  • Infant
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors / complications*
  • Lipid Metabolism, Inborn Errors / metabolism
  • Lipid Metabolism, Inborn Errors / pathology
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Neonatal Screening / methods
  • Oxidation-Reduction
  • Retrospective Studies
  • Sudden Infant Death / etiology*
  • Sudden Infant Death / pathology

Substances

  • Fatty Acids
  • Glutarates
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Acyl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase, Long-Chain
  • glutaric acid
  • Carnitine