title: Combination of postmortem mass spectrometry imaging and genetic analysis reveals very long-chain acyl-CoA dehydrogenase deficiency in a case of infant death with liver steatosis.
abstract: METHODS
  A 3-month-old infant was found dead in his bed. A postmortem computed tomography (CT) scan suggested fatty attenuation in the liver parenchyma, but no other potentially fatal changes were found. To clarify the cause of death, a medicolegal autopsy was carried out.
  Internal examination confirmed the presence of liver steatosis as well as hepatomegaly. There were no other significant findings including encephalitis or brain edema.
  To clarify the mechanism underlying lipid accumulation in the liver, matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) analysis was conducted. This indicated a significant accumulation of C14:1 acylcarnitine in the liver of the deceased, suggesting very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency.
  To find the cause of the VLCAD deficiency, genetic analysis of the responsible gene, acyl-CoA dehydrogenase, very long chain (ACADVL), was performed. This revealed two novel mutations that may have accounted for the disease.
  
  
  CONCLUSIONS
  A combination of these data revealed that the liver steatosis in this case might have been caused by VLCAD deficiency based on genetic mutations of ACADVL. Thus, the deceased might have been vulnerable to energy crisis and sudden infant death. The present findings show that MALDI-IMS analysis as well as genetic analysis can be useful for elucidating the cause of death.
authors.affiliation: Department of Legal Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Legal Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Sano
authors.affiliation: Department of Legal Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Department of Legal Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan. Electronic address: kominato@gunma-u.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kominato
authors.affiliation: Department of Legal Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Kubo
authors.affiliation: Department of Legal Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Biochemistry, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Ohshima
authors.affiliation: Laboratory for Analytical Instruments, Education and Research Support Center, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Tohko
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tokue
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Awata
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirasawa
authors.affiliation: Department of Pediatrics, Gunma University Hospital, Maebashi 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishige
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency* / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D000080984:Congenital Bone Marrow Failure Syndromes; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D053803:Forensic Genetics; D049429:Forensic Pathology; D006529:Hepatomegaly / Q000473:pathology; D006801:Humans; D007223:Infant; D007564:Japan; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis*; D008297:Male; D028361:Mitochondrial Diseases / Q000175:diagnosis*; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000175:diagnosis*; D009154:Mutation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D044942:Acyl-CoA Dehydrogenase, Long-Chain; C467805:ACADVL protein, human
keywords: Fatty acid oxidation; Imaging mass spectrometry; Liver steatosis; Sudden infant death