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Systematic review and meta-analysis to estimate the birth prevalence of five inherited metabolic diseases


Many newborn screening programmes now use tandem mass spectrometry in order to screen for a variety of diseases. However, countries have embraced this technology with a differing pace of change and for different conditions. This has been facilitated by the ability of this diagnostic method to limit analysis to specific metabolites of interest, enabling targeted screening for particular conditions. MS/MS was introduced in 2009 in England to implement newborn bloodspot screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) raising the possibility of screening for other inherited metabolic disorders. Recently, a pilot screening programme was conducted in order to evaluate the health and economic consequences of screening for five additional inherited metabolic disorders in England. As part of this study we conducted a systematic review and meta-analysis to estimate the birth prevalence of these conditions: maple syrup urine disease, homocystinuria (pyridoxine unresponsive), glutaric aciduria type I, isovaleric acidaemia and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency including trifunctional protein deficiency. We identified a total of 99 studies that were able to provide information on the prevalence of one or more of the disorders. The vast majority of studies were of screening programmes with some reporting on clinically detected cases.

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Fig. 1
Fig. 2



Glutaric aciduria type 1




Health technology assessment


Inherited metabolic disease


Isovaleric acidaemia


Long chain 3-hydroxy acyl-CoA dehydrogenase deficiency


Medium chain acyl-CoA dehydrogenase deficiency


Tandem mass spectrometry


Maple syrup urine disease


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The authors would like to acknowledge with thanks the laboratories who contributed data for this report.

Conflict of interest

Sowmiya Moorthie Louise Cameron, Gurdeep S Sagoo, Jim Bonham and Hilary Burton declare they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.


This review was funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for South Yorkshire (NIHR CLAHRC SY).

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Corresponding author

Correspondence to Sowmiya Moorthie.

Additional information

Communicated by: Bridget Wilcken

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Moorthie, S., Cameron, L., Sagoo, G.S. et al. Systematic review and meta-analysis to estimate the birth prevalence of five inherited metabolic diseases. J Inherit Metab Dis 37, 889–898 (2014).

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  • Newborn Screening
  • Western Population
  • Congenital Hypothyroidism
  • Homocystinuria
  • Maple Syrup Urine Disease