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Screening for organic acidurias and amino acidopathies in newborns and children

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Journal of Inherited Metabolic Disease

Abstract

This investigation was undertaken in order to define the place of multidisease screening for inborn errors of metabolism in paediatric practice with particular reference to the organic acidurias, and to compare the efficiency of organic acid screening as a detection method for inborn errors of metabolism with that of amino acid screening on urine. The clinical criteria adopted for the selection of patients were: (i) acute unexplained illness in the newborn or infant; (ii) unexplained developmental delay in infancy or early childhood.

The derivatized organic acids were separated by automated gas chromatography and identified by mass spectrometry. The patients were also screened for abnormal amino acidurias by thin-layer chromatography supplemented by automated quantitative column chromatography when visual inspection of the thin-layer chromatography plates suggested that the result might be abnormal.

Six hundred and ninety-five patients were studied. The incidence of abnormalities was higher in the material which was referred from other hospitals. We attribute this to the more extensive preliminary investigation to which these cases had been subjected before our help was sought than was the case in patients referred from our hospital.

We conclude that screening for organic acidurias on the basis of the broad criteria which we originally specified is unproductive and not cost-effective and that screening for organic acidurias should be confined to acutely ill neonates and young children who have been systematically evaluated biochemically by other means. A suitable scheme of investigation which need not involve a clinically unacceptable delay is proposed.

Organic acid analysis by the present methods detected about ten times more abnormalities than amino acid analysis, or three times more if one considers only the known and likely inherited metabolic abnormalities in this series. The amino acidopathies were often diagnosed more precisely by the associated organic aciduria and only a few of the known inborn errors of metabolism require amino acid analysis exclusively for their identification. The present type of urinary organic acid analysis used as part of the investigation scheme which we have described will identify about one third of the approximately 180 inherited metabolic diseases with known enzyme defects. Organic acid analysis also detects other disorders and usually provides more information about the underlying biochemical derangement than does amino acid analysis alone.

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Authors and Affiliations

  1. Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Watford Road, HA1 3UJ, Harrow, Middlesex

    R. A. Chalmers, P. Purkiss & R. W. E. Watts

  2. Division of Clinical Chemistry, MRC Clinical Research Centre, Watford Road, HA1 3UJ, Harrow, Middlesex

    A. M. Lawson

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  1. R. A. Chalmers
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  2. P. Purkiss
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  3. R. W. E. Watts
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  4. A. M. Lawson
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Additional information

We are most grateful also to our colleagues who have very generously, over several years, sent reference specimens from their patients with identified inherited metabolic diseases for comparison and study by our methods, particularly Dr S. K. Wadman and Dr M. Duran, Wilhelmina Kinderziekenhuis, Utrecht, Dr N. J. Brandt and Dr E. Christensen, Rigshospitalet. Copenhagen. Dr K. Rasmussen and Dr N. Gregersen, århus Kommunehospital. Dr N. Kennaway. University of Oregon, Dr K. Tanaka. Yale University School of Medicine, Dr V. G. Oberholzer, Queen Elizabeth Hospital for Children, Hackney, and Dr D. Gompertz. formerly at Hammersmith Hospital, London.

These studies were approved by the Ethical Committee of Northwick Park Hospital and the Clinical Research Centre.

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Chalmers, R.A., Purkiss, P., Watts, R.W.E. et al. Screening for organic acidurias and amino acidopathies in newborns and children. J Inherit Metab Dis 3, 27–43 (1980). https://doi.org/10.1007/BF02312520

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  • DOI: https://doi.org/10.1007/BF02312520

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