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Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting

  • Fatty Acid Oxidation
  • Published:
Journal of Inherited Metabolic Disease

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Abstract

Experience with new-born screening (NBS) for disorders of fatty-acid oxidation (FAOD) is now becoming available from an increasing number of programs worldwide. The spectrum of FAOD differs widely between ethnic groups. Incidence calculations from reports from Australia, Germany, and the USA of a total of 5,256,999 newborns give a combined incidence of all FAOD of approximately 1:9,300. However, it appears to be much lower in Asians. Consequently, a significant prevalence and evidence for a clear benefit of NBS is proven for medium-chain acyl-CoA dehydrogenase deficiency (MCAD) only in countries with a high percentage of Caucasians, with very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) and long-chain 3-hydroxy acyl-CoA dehydrogenase deficiency (LCHAD) being additional candidates. The long-term benefit for many disorders has still to be evaluated and will require international collaboration, especially for the rarest disorders. Short-chain acyl-CoA dehydrogenase deficiency (SCAD) [as well as Systemic carnitine transporter deficiency (CTD) and dienoyl-CoA reductase deficiency (DE-RED)] are conditions of uncertain clinical significance, but most FAOD have a spectrum of clinical presentations (healthy–death). Confirmatory diagnostic procedures should be agreed upon to ensure international comparability of results and evidence-based modifications. The case of short-chain acyl-CoA dehydrogenase deficiency (SCAD) deficiency shows that even inclusion of conditions without a clearly known natural course may prove useful with respect to gain of knowledge and consecutive exclusion of a biochemical abnormality without clinical significance, although this line of argument implies the existence of structured follow-up programs and bears ethical controversies. As a final conclusion, the accumulated evidence suggests all FAOD should to be included into tandem mass spectrometry (MS/MS)-based NBS programs provided sufficient laboratory performance is guaranteed.

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Abbreviations

NBS:

Newborn screening

FAOD:

Fatty-acid oxidation disorders

MCAD:

Medium-chain acyl-CoA dehydrogenase deficiency

VLCAD:

Very-long-chain acyl-CoA dehydrogenase deficiency

LCHAD/mTFP:

Long-chain 3-hydroxy acyl-CoA dehydrogenase deficiency/mitochondrial trifunctional protein deficiency

CTD:

Systemic carnitine transporter deficiency

SCAD:

Short-chain acyl-CoA dehydrogenase deficiency

CPT I:

Carnitine palmitoyltransferase 1 deficiency

CPT II:

Carnitine palmitoyltransferase-2 deficiency

CACT:

Carnitine acylcarnitine translocase deficiency

MAD/GA II:

Multiple acyl-CoA dehydrogenase deficiency/glutaric aciduria type II (synonym)

MCKAT:

Medium-chain ketothiolase

M/SCHAD:

Medium-/short-chain 3-OH-acyl-CoA dehydrogenase deficiency

DE-RED:

Dienoyl-CoA reductase deficiency

MS/MS:

Tandem mass spectrometry

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Acknowledgements

We thank all colleagues who participated and contributed to the discussion, especially Dr. Olaf Bodamer, Austria, Dr. Andreas Schulze, Canada, Dr. Ute Spiekerkötter, Germany, and Dr. Bridget Wilcken, Australia. The work of Dr. Lindner and Dr. Hoffmann is generously sponsored by the Dietmar-Hopp-Stiftung, Walldorf GmbH.

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Authors and Affiliations

  1. University Children’s Hospital, INF 430, 69124, Heidelberg, Germany

    Martin Lindner & Georg F. Hoffmann

  2. Mayo Clinic, College of Medicine, Rochester, MN, USA

    Dietrich Matern

Authors
  1. Martin Lindner
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  2. Georg F. Hoffmann
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  3. Dietrich Matern
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Corresponding author

Correspondence to Martin Lindner.

Additional information

Communicated by: Verena Peters

Competing interest: None declared.

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Lindner, M., Hoffmann, G.F. & Matern, D. Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting. J Inherit Metab Dis 33, 521–526 (2010). https://doi.org/10.1007/s10545-010-9076-8

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  • DOI: https://doi.org/10.1007/s10545-010-9076-8

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