title: Tandem mass spectrometry findings at autopsy for detection of metabolic disease in infant deaths: postmortem changes and confounding factors.
abstract: OBJECTIVE
  Tandem mass spectrometry (MS/MS) is a recommended investigation for sudden unexpected death in infancy (SUDI), but there are limited data regarding yield and potential influencing factors. This study investigates postmortem acylcarnitine profiles in a large cohort of infant deaths from a single centre, including those with metabolic disease.
  
  
  METHODS
  Acylcarnitine results obtained by MS/MS from routine blood/bile spot samples during the standard autopsy investigation were identified from infant deaths over a 14-year period. Results were categorised as normal or abnormal according to the clinical report by a specialist paediatric biochemist. Possible interdependent variables were assessed, multiple linear regression models were constructed and residual comparison was undertaken.
  
  
  RESULTS
  397 blood and 268 bile MS/MS results were identified from infant cases, including 255 matched blood-bile pairs. There was significant association between blood acylcarnitine findings and postmortem interval (PMI), body mass index and liver weight. A probable cause of death was identified in 40% of sudden death cases, including 18 (2%) with a definite or highly likely cause of death as underlying metabolic disease; this represented 12 (12%) unexpected deaths in the first week of life and six (<1%) aged 7-365 days. Fatty acid oxidation disorders identified included very long chain acyl-CoA dehydrogenase deficiency, medium chain acyl-CoA dehydrogenase deficiency and carnitine transporter defects.
  
  
  CONCLUSIONS
  Postmortem blood and bile acylcarnitine profiles are influenced by several variables, and PMI can influence MS/MS acylcarnitine results. Metabolic disease may present as SUDI and may be identified from postmortem samples.
authors: UCL Institute of Child Health, Great Ormond Street Hospital for Children, London, UK.
authors: J W
authors: JW
authors: Pryce
authors: M A
authors: MA
authors: Weber
authors: S
authors: S
authors: Heales
authors: M
authors: M
authors: Malone
authors: N J
authors: NJ
authors: Sebire
mesh_terms: D001344:Autopsy / Q000379:methods*; D001646:Bile / Q000737:chemistry; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology; D008659:Metabolic Diseases / Q000097:blood / Q000473:pathology*; D009929:Organ Size; D011180:Postmortem Changes; D013398:Sudden Infant Death / Q000473:pathology*; D053719:Tandem Mass Spectrometry
chemical_list: C116917:acylcarnitine; D002331:Carnitine