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Elevation of pivaloylcarnitine by sivelestat sodium in two children

Kenji Yamada1, Hironori Kobayashi1, Ryosuke Bo2

  • 1Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan.

Molecular Genetics and Metabolism
|October 3, 2015
PubMed

Insights

Sivelestat treatment can cause elevated C5-acylcarnitine levels, mimicking isovaleric acidemia in newborns. This occurs due to pivalic acid in sivelestat, potentially leading to secondary carnitine deficiency.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Neonatal Medicine

Background:

  • Sivelestat sodium, a neutrophil elastase inhibitor, is utilized for treating acute respiratory distress syndrome (ARDS).
  • This report details two cases where elevated C5-acylcarnitine (C5-AC) levels were observed following sivelestat administration.
  • One case involved a premature infant treated for Wilson-Mikity syndrome, and the other a child with pneumocystis pneumonia and ARDS.

Observation:

  • Elevated C5-AC levels were detected in both patients after sivelestat treatment.
  • Isovaleric acidemia (IVA) was initially suspected in the infant due to high C5-AC levels detected via newborn screening.
  • Urinary organic acid analysis ruled out IVA, but elevated pivaloylcarnitine (PVC) was confirmed in both cases.

Findings:

  • Sivelestat contains pivalic acid (PVA), similar to certain antibiotics.
  • PVA is known to potentially induce secondary carnitine deficiency.
  • Elevated PVC levels can lead to false positive results for IVA in newborn screening using tandem mass spectrometry (MS/MS).

Implications:

  • The findings highlight a potential diagnostic challenge in newborn screening for metabolic disorders.
  • Clinicians should consider sivelestat's pivalic acid component when interpreting elevated C5-AC levels.
  • This underscores the importance of considering drug-induced metabolic alterations in patient management.
Abstract

Keywords:
Antibiotics containing pivalic acidIsovaleric acidemiaNewborn screeningPivaloylcarnitineSivelestat sodiumTandem mass spectrometry

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