Molecular diagnosis for a fatal case of very long-chain acyl-CoA dehydrogenase deficiency in Hong Kong Chinese with a novel mutation: a preventable death by newborn screening

Diagn Mol Pathol. 2012 Sep;21(3):184-7. doi: 10.1097/PDM.0b013e31825554d0.


Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the most common fatty acid oxidation defects that cause sudden unexpected deaths in infants. The death attributed to VLCAD deficiency can be prevented by early diagnosis with expanded newborn screening using tandem mass spectrometry. A favorable outcome can be achieved with early diagnosis and prompt treatment. However, such newborn screening has not yet been available in Hong Kong. We report a 2-month-old boy who succumbed 5 hours after admission with the diagnosis of VLCAD deficiency confirmed by genetic analysis performed after death. The patient was compound heterozygous for a novel splicing mutation ACADVL NM_000018.2:c.277+2T>G; NC_000017.10:g.7123997T>G and a known disease-causing mutation ACADVL NM_000018.2:c.388_390del; NP_000009.1: p.Glu130del. Family screening was performed for at-risk siblings. The rapid downhill course of the patient clearly illustrates the need of newborn screening for early diagnosis. Our patient was asymptomatic before metabolic decompensation. However, once metabolic decompensation occurred, rapid deterioration and death followed, which obviated the opportunity to diagnose and treat. The only way to save these patients' lives and improve their outcome is early diagnosis and appropriate treatment. Therefore, we strongly urge the implementation of newborn screening using tandem mass spectrometry for VLCAD deficiency and other highly treatable inborn errors of metabolism in Hong Kong.

Publication types

  • Case Reports

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / blood
  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency
  • Acyl-CoA Dehydrogenase, Long-Chain / genetics*
  • Congenital Bone Marrow Failure Syndromes
  • Fatal Outcome
  • Heterozygote
  • Hong Kong
  • Humans
  • Infant
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors / diagnosis*
  • Lipid Metabolism, Inborn Errors / genetics
  • Lipid Metabolism, Inborn Errors / prevention & control
  • Male
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / prevention & control
  • Muscular Diseases / diagnosis*
  • Muscular Diseases / genetics
  • Muscular Diseases / prevention & control
  • Mutation
  • Neonatal Screening*
  • RNA Splicing / genetics
  • Sequence Analysis, DNA
  • Siblings
  • Tandem Mass Spectrometry


  • Acyl-CoA Dehydrogenase, Long-Chain
  • ACADVL protein, human

Supplementary concepts

  • VLCAD deficiency