Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life.
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.


METHODS
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.


CONCLUSIONS
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.
Boles
R G
RG
Department of Genetics and Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8005, USA.
Buck
E A
EA
Blitzer
M G
MG
Platt
M S
MS
Cowan
T M
TM
Martin
S K
SK
Yoon
H
H
Madsen
J A
JA
Reyes-Mugica
M
M
Rinaldo
P
P
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency; D002331:Carnitine / Q000378:metabolism; D016022:Case-Control Studies; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005977:Glutarates / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D010084:Oxidation-Reduction; D012189:Retrospective Studies; D013398:Sudden Infant Death / Q000209:etiology* / Q000473:pathology
D005227:Fatty Acids; D005977:Glutarates; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; C035736:glutaric acid; D002331:Carnitine