Diagnostic potential of stored dried blood spots for inborn errors of metabolism: A metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency

Noriyuki Kaku, Kenji Ihara, Yuichiro Hirata, Kenji Yamada, Sooyoung Lee, Hikaru Kanemasa, Yoshitomo Motomura, Haruhisa Baba, Tamami Tanaka, Yasunari Sakai, Yoshihiko Maehara, Shoichi Ohga

研究成果: ジャーナルへの寄稿記事

抄録

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.

元の言語英語
ページ(範囲)885-889
ページ数5
ジャーナルJournal of Clinical Pathology
71
発行部数10
DOI
出版物ステータス出版済み - 10 1 2018

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Inborn Errors Metabolism
Autopsy
Molecular Biology
Cause of Death
Newborn Infant
Sudden Infant Death
Tandem Mass Spectrometry
Japan
Medium chain acyl CoA dehydrogenase deficiency
acylcarnitine

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

これを引用

Diagnostic potential of stored dried blood spots for inborn errors of metabolism : A metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency. / Kaku, Noriyuki; Ihara, Kenji; Hirata, Yuichiro; Yamada, Kenji; Lee, Sooyoung; Kanemasa, Hikaru; Motomura, Yoshitomo; Baba, Haruhisa; Tanaka, Tamami; Sakai, Yasunari; Maehara, Yoshihiko; Ohga, Shoichi.

:: Journal of Clinical Pathology, 巻 71, 番号 10, 01.10.2018, p. 885-889.

研究成果: ジャーナルへの寄稿記事

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abstract = "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.",
author = "Noriyuki Kaku and Kenji Ihara and Yuichiro Hirata and Kenji Yamada and Sooyoung Lee and Hikaru Kanemasa and Yoshitomo Motomura and Haruhisa Baba and Tamami Tanaka and Yasunari Sakai and Yoshihiko Maehara and Shoichi Ohga",
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T1 - Diagnostic potential of stored dried blood spots for inborn errors of metabolism

T2 - A metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency

AU - Kaku, Noriyuki

AU - Ihara, Kenji

AU - Hirata, Yuichiro

AU - Yamada, Kenji

AU - Lee, Sooyoung

AU - Kanemasa, Hikaru

AU - Motomura, Yoshitomo

AU - Baba, Haruhisa

AU - Tanaka, Tamami

AU - Sakai, Yasunari

AU - Maehara, Yoshihiko

AU - Ohga, Shoichi

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

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