Post-mortem analysis for two prevalent β-oxidation mutations in sudden infant death
Article first published online: 31 OCT 2007
Volume 49, Issue 6, pages 883–887, December 2007
How to Cite
YANG, Z., LANTZ, P. E. and IBDAH, J. A. (2007), Post-mortem analysis for two prevalent β-oxidation mutations in sudden infant death. Pediatrics International, 49: 883–887. doi: 10.1111/j.1442-200X.2007.02478.x
- Issue published online: 31 OCT 2007
- Article first published online: 31 OCT 2007
- Received 30 October 2004; revised 4 September 2006; accepted 19 October 2006; published online: 31 October 2007.
- mitochondrial trifunctional protein;
- sudden infant death (SID)
Background: Fatty acid oxidation disorders may cause sudden and unexpected infant death and are associated with the histological hallmark of hepatic steatosis. The goal of the present study was to assess the value of post-mortem molecular analysis for medium-chain acyl-coenzyme A dehydrogenase (MCAD) and mitochondrial trifunctional protein (MTP) defects in unexplained sudden infant death (SID) associated with fatty infiltration of the liver. MCAD catalyzes the first step of medium-chain fatty acid oxidation while MTP catalyzes the last three steps of long-chain fatty acid oxidation.
Methods: In a retrospective study, 220 consecutive cases of sudden and unexplained infant death certified by medical examiners at Wake Forest University Medical Center were assessed for hepatic steatosis. Subjects with evidence of hepatic steatosis were screened for mutations in MCAD and MTPα-subunit using DNA isolated from paraffin-embedded liver tissue, single-strand conformation variance, and nucleotide sequence analyses.
Results: Sixteen cases (7.3%) were associated with diffuse micro-vesicular or mixed micro- and macro-vesicular hepatic steatosis. Two of these 16 cases (12.5%) had disease-causing mutations. One was homozygous for the prevalent MCAD A985G mutation. The second was a compound heterozygous for the prevalent MTP G1528C mutation and a novel 1 bp deletion in exon 18 of the MTPα-subunit gene.
Conclusions: A significant proportion (7.3%) of SID is associated with hepatic steatosis. The present data support post-mortem molecular analysis for the MCAD A985G and MTP G1528C prevalent mutations in cases of sudden and unexplained infant death associated with hepatic steatosis.