title: Elevation of pivaloylcarnitine by sivelestat sodium in two children.
abstract: BACKGROUND
  Sivelestat sodium (sivelestat), a neutrophil elastase inhibitor, is used to treat acute respiratory distress syndrome (ARDS). We report two cases that developed elevated C5-acylcarnitine (C5-AC) levels following treatment with sivelestat. Case 1 was a 14-day-old female infant born at 25 weeks and 1 day of gestation who was treated with sivelestat for the prophylaxis of Wilson-Mikity syndrome soon after birth. Isovaleric acidemia (IVA) was suspected based on a newborn screening using tandem mass spectrometry (MS/MS). Her C5-AC level was elevated to 4.49 μM (cut-off, <1.0) after treatment with sivelestat. Case 2 was a 4-year-old female with pneumocystis pneumonia that developed during chemotherapy for disseminated medulloblastoma. Sivelestat was given for the complication of ARDS. Her C5-AC level increased (1.09 μM) after eight days of treatment with sivelestat.
  
  
  RESULTS
  In both cases, IVA was ruled out because isovalerylglycine was not observed in the urinary organic acid analysis. Case 1 was associated with carnitine deficiency (C0 9.16 μM; reference value, 10-60). Liquid chromatography-MS/MS confirmed elevated pivaloylcarnitine (PVC) in both cases.
  
  
  CONCLUSIONS
  Similar to antibiotics containing pivalic acid (PVA), sivelestat contains PVA, which has the potential to cause secondary carnitine deficiency. In addition, elevated PVC can lead to false positive findings of IVA in newborns screened using MS/MS.
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan. Electronic address: k-yamada@med.shimane-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan; Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Bo
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Neonatology, Okayama Medical Center, 1711-1 Tamasu, Kita-ku, Okayama 701-1192, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Tokyo Health Service Association, 1-2 Ichigayasadoharacho, Shinjuku-ku, Tokyo 162-8402, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishige
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis; D009202:Cardiomyopathies / Q000150:complications; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency; D002675:Child, Preschool; D002853:Chromatography, Liquid; D005260:Female; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000150:complications; D007231:Infant, Newborn; D050769:Isovaleryl-CoA Dehydrogenase / Q000172:deficiency; D009135:Muscular Diseases / Q000150:complications; D015997:Neonatal Screening; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C116917:acylcarnitine; C054040:pivaloylcarnitine; C069195:sivelestat; D050769:Isovaleryl-CoA Dehydrogenase; D002331:Carnitine; D005998:Glycine
keywords: Antibiotics containing pivalic acid; Isovaleric acidemia; Newborn screening; Pivaloylcarnitine; Sivelestat sodium; Tandem mass spectrometry