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Tandem mass spectrometry findings at autopsy for detection of metabolic disease in infant deaths: postmortem changes and confounding factors
  1. J W Pryce1,
  2. M A Weber2,
  3. S Heales1,3,
  4. M Malone2,
  5. N J Sebire1,2
  1. 1UCL Institute of Child Health, Great Ormond Street Hospital for Children, London, UK
  2. 2Department of Histopathology, Great Ormond Street Hospital for Children, London, UK
  3. 3Department of Chemical Patholgy, Great Ormond Street Hospital for Children, London, UK
  1. Correspondence to Professor N J Sebire, Department of Histopathology, Camelia Botnar Laboratories, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK; sebirn{at}gosh.nhs.uk

Abstract

Aim 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.

Conclusion 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.

  • Autopsy
  • autopsy pathology
  • histopathology
  • infant death
  • metabolic
  • neoplasms
  • neuroblastoma
  • paediatric pathology
  • placenta
  • postmortem
  • SIDS
  • tandem mass spectrometry
  • trophoblastic disease
  • yes

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Footnotes

  • Funding JWP is funded by a grant awarded by SPARKS charity. SPARKS had no involvement in the collection, analysis or interpretation of data, in the writing of this paper, or in the decision to submit the paper for publication. JWP and NJS ensure the veracity and integrity of this study.

  • Competing interests None to declare.

  • Ethics approval Local research ethics committee approval has been granted. Great Ormond Street Hospital Local Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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