Intended for healthcare professionals


Screening for medium chain acyl-CoA dehydrogenase deficiency has still not been evaluated

BMJ 2001; 322 doi: (Published 13 January 2001) Cite this as: BMJ 2001;322:112
  1. Stuart Tanner (m.s.tanner{at}, professor of child health,
  2. Mark Sharrard, consultant paediatrician with a special interest in metabolic disease,
  3. Maureen Cleary, consultant paediatrician with special interest in metabolic disease,
  4. John Walter, consultant paediatrician with special interest in metabolic disease,
  5. Ed Wraith, consultant paediatrician with special interest in metabolic disease,
  6. Philip Lee, consultant paediatrician/metabolic medicine,
  7. James Leonard, professor of paediatric metabolic disease,
  8. Andrew Morris, senior lecturer in paediatric metabolic medicine,
  9. Neil McIntosh, professor of child life and health
  1. University of Sheffield
  2. Sheffield Children's Hospital, Sheffield S10 2TH
  3. Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester M27 4HA
  4. Charles Dent Metabolic Unit, National Hospital for Neurology, Queen Square, London WC1N 3BG
  5. Biochemistry, Endocrinology and Metabolism, Institute of Child Health, London WC1N 1EH
  6. Sir James Spence Department of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP
  7. University of Edinburgh, Edinburgh EH9 1UW

    EDITOR—Every baby born in the United Kingdom is screened for phenylketonuria and congenital hypothyroidism at 6-14 days of age. Several screening laboratories now use tandem mass spectrometry for estimating blood phenylalanine concentration. Tandem mass spectrometry can assay simultaneously, in the same sample, many other metabolites and can thus potentially detect other metabolic disorders, including medium chain acyl-CoA dehydrogenase deficiency.

    Medium chain acyl-CoA dehydrogenase deficiency is almost as common as phenylketonuria, affecting roughly 1:15 000 births in the United Kingdom. Infants with the deficiency are well until challenged by a catabolic stress, most commonly a mild intercurrent infection or fasting. As a result of the acute encephalopathy, affected infants may die or be left with profound neurological damage. Undiagnosed, medium chain acyl-CoA dehydrogenase deficiency has a mortality of up to 20%, and 10-15% are left severely handicapped. But early treatment is simple, cheap, and effective. Among 41 patients treated in one centre for a median of 6.7 years there were no additional deaths even though the incidence of previous death among siblings was high.1

    A possible concern about screening is the anxiety caused to parents whose infants with medium chain acyl-CoA dehydrogenase deficiency never become ill because they are never challenged. But it is indefensible to withhold the knowledge that the child is at an easily avoided risk. It is sometimes thought that we can rely on clinical acuity to diagnose the deficiency before severe damage occurs, but the non-specific features of the encephalopathy make this an ineffective strategy. The extra cost of screening for the deficiency is less than £1 per baby.

    Two systematic reviews commissioned by the health technology assessment programme in 1993 recommended further studies on the application of tandem mass spectrometry to neonatal screening. 2 3 In keeping with the ethos that all screening programmes should be evaluated, a moratorium on the introduction of screening for medium chain acyl-CoA dehydrogenase deficiency was agreed pending pilot studies. The failure to fund these studies, however, has led to considerable frustration among all those involved. There is a risk that screening will be introduced without trials, as is already occurring in parts of Germany, Australia, and the United States. The opportunity for a structured evaluation may be missed.

    Prevention is one of the challenges laid down in the National Plan for the NHS, but the health technology assessment process has failed in this case. The challenge now is how to move forward responsibly.


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