Elevation of pivaloylcarnitine by sivelestat sodium in two children

Mol Genet Metab. 2015 Nov;116(3):192-4. doi: 10.1016/j.ymgme.2015.09.009. Epub 2015 Sep 26.

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.

Discussion: 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.

Keywords: Antibiotics containing pivalic acid; Isovaleric acidemia; Newborn screening; Pivaloylcarnitine; Sivelestat sodium; Tandem mass spectrometry.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Cardiomyopathies / complications
  • Carnitine / analogs & derivatives*
  • Carnitine / blood
  • Carnitine / deficiency
  • Child, Preschool
  • Chromatography, Liquid
  • Female
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Humans
  • Hyperammonemia / complications
  • Infant, Newborn
  • Isovaleryl-CoA Dehydrogenase / deficiency
  • Muscular Diseases / complications
  • Neonatal Screening
  • Serine Proteinase Inhibitors / adverse effects*
  • Serine Proteinase Inhibitors / therapeutic use*
  • Sulfonamides / adverse effects*
  • Sulfonamides / therapeutic use*
  • Tandem Mass Spectrometry

Substances

  • Serine Proteinase Inhibitors
  • Sulfonamides
  • acylcarnitine
  • pivaloylcarnitine
  • sivelestat
  • Isovaleryl-CoA Dehydrogenase
  • Carnitine
  • Glycine

Supplementary concepts

  • Acidemia, isovaleric
  • Systemic carnitine deficiency