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Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency
  1. Noriyuki Kaku1,2,
  2. Kenji Ihara1,3,
  3. Yuichiro Hirata1,2,
  4. Kenji Yamada4,
  5. Sooyoung Lee1,2,
  6. Hikaru Kanemasa1,
  7. Yoshitomo Motomura1,2,
  8. Haruhisa Baba1,2,
  9. Tamami Tanaka1,
  10. Yasunari Sakai1,
  11. Yoshihiko Maehara2,
  12. Shouichi Ohga1
  1. 1 Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  2. 2 Emergency and Critical Care Center, Kyushu University Hospital, Fukuoka, Japan
  3. 3 Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Japan
  4. 4 Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Japan
  1. Correspondence to Professor Kenji Ihara, Department of Pediatrics, Oita University Faculty of Medicine, Yufu 879-5593, Japan; k-ihara{at}


Aim It is estimated that 1–5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly.

Methods Infants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Their Guthrie cards, which had been stored for several years at 4–8°C, were used for an acylcarnitine analysis by tandem mass spectrometry to identify inborn errors of metabolism.

Results Fifteen infants and children who died at less than 2 years of age and for whom the cause of death was unknown were enrolled for the study. After correcting the C0 and C8 values assuming the hydrolysation of acylcarnitine in the stored DBSs, the corrected C8 value of one case just exceeded the cut-off level for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening. Genetic and biochemical analyses confirmed this patient to have MCAD deficiency.

Conclusion DBSs stored after newborn screening tests are a promising tool for metabolic autopsy. The appropriate compensation of acylcarnitine data and subsequent genetic and biochemical analyses are essential for the postmortem diagnosis of inborn errors of metabolism.

  • metabolism
  • sids
  • newborn biochemical screening

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  • Handling editor Tahir S Pillay.

  • Contributors NK and KI contributed to the study conception and design; NK, YH, SL and HB were involved in the treatment of the patients and data collection; KY, HK YM, TT and YS were involved in the metabolic and gene analysis and provided conceptual advice; NK drafted the manuscript; YM and SO critically reviewed the manuscript and supervised the whole study process.

  • Funding The work was supported in part by JSPS KAKENHI grant number JP17K12349 (N. Kaku).

  • Competing interests None declared.

  • Patient consent Parental/guardian consent obtained.

  • Ethics approval This study was approved by the ethics committee of Kyushu University Hospital, Fukuoka, Japan (No. 25-105).

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